Having finished the game and explored every corner, I feel like the game leaves a lot of unexplained mysteries. I haven't bought the sequel yet, but looking over the game page my guess is that it might answer questions about some of the characters and their backstories but is unlikely to answer questions about the events of this game.
What follows will contain massive amounts of spoilers. Don't read unless you are totally done with the game. In fact, I'm going to pad this disclaimer with some more sentences so that you have to hit "view rest" to see the spoilers. Does that vary depending on the size of your screen? I don't know, but I may as well try. It is not like a couple extra lines are going to break anything.
Edit: Okay, even more lines, since the author confirms that he sees part of the first question even after I added enough for it to not show up on my screen. Not that it will be possible bury things for everyone. When I checked on my phone, the comment didn't collapse at all. But I can at least reduce the proportion of users who see spoilers without needing to click on something.
1. In the true ending, Emily says that Simon should not be remembering past attempts and it must be the influence of the observer. But if that's the case, then what is with the lock leading to the true end? Based on the message on the remote, it sounds like she was counting on him waking her up so he could forgive her, and that fits with giving out three of the letters in the three runs leading up to the final one as she realizes she needs to wrap things up before she dies of old age, but all of that is pointless if Simon can't remember the clues. And Emily personally telling Simon one of the letters in ending A seems especially weird, since it doesn't sound like Emily had even decided on running the game over and over until the aftermath of A.
2. In ending A, Agnos claims that the scanners are broken, which is tested by throwing dead people's collars through them. But there are enough functioning sensors to close the door after two go through, and actually all eight collars are paired off correctly to let everyone get through. This seems like it is supposed to suggest that the scanners are working fine, and it only seemed broken because Agnos happened to choose the right ones to go together. But if we aren't dealing with widespread security system failures, then that raises the question of why we (and Agnos) weren't killed for bringing too many collars into a room. I had a thought that A had four collars in a room while the executions involved only three, which could fit with Smiley saying that people must travel in pairs (dating game), but checking back she specifically said "you are forbidden to enter the staircase with more than one partner". That means the groups of four are more clear of a violation than the actual executions, where one person made it out of the stairway before the next two came in.
3. Where does Ray get the gun in the orange route? Guns are established as being in the pantry and gym. In that route, he only goes to the dorm before pulling out the gun. Did he get one from Agnos somehow? Agnos was knocked out, and his cut off comment could make sense if he found someone else packing heat and took it. Is Emily changing around the locations of the guns? Did Emily swap the A/E and Ray/J explorations this route, only for Simon to have incorrect memories (like the pink route)? Are there more guns hidden around that just go unused most of the time? When Simon explores the dorms with Ray, there was the scene where Ray hides something then it turns out to be two sandwiches, only for Ray to be paranoid about poison... did he pretend he wanted both sandwiches to cover up that he was actually hiding a gun that came with them? Ray knocked out Agnos and took his gun.
4. In ending F, Simon wonders what he should tell Greta, but H never said that name in that ending. She did reveal it in ending E, which is chronologically earlier then F, but then we're back to Emily saying that Simon shouldn't be remembering past routes. If it is the influence of the observer, then shouldn't it be based on what the player has seen, which doesn't necessarily include ending E? I did notice the ending P has Simon reference in mediAS res which is chronologically part of ending R, supporting the theory that the bleed-through is based on what the player has seen rather than what has happened so far in universe.
5. What would happen if four people took the train to the theater or reactor? I would have guessed that after two get off the train would be rotated without going up a floor, but for some reason Simon (in ending P) seems to think it would be impossible to be on the train when it starts going in that direction. Ending H shows that the train refuses to move on until empty even though the theater is closed, but the closure is due to rubble so it may not be a good example.
6. What happens if you take the elevator to floor -13? If I understand correctly, this should be the lounge, but the lounge has no scanner room. Does the elevator have an extra button just because they didn't want a gap in the numbering? Is there a secret room accessible only by elevator? Is there a hidden door in the lounge bathroom leading to the elevator? Even when the scanner room in the dorm was hidden, you can see it on the map (although it actually looks like the mirror should lead towards one of the bathrooms, with the entrance to the scanner room being offscreen), but there's nothing on the lounge map.
7. Why does H freak out about the 'H word' while J does not? Is she protected by not fully having the relevant memories (except in routes where the word never comes up)?
8. What did J see in the security room? I checked the other time Simon visits the security room, but the other screens are turned off and he doesn't try to turn them on, so all I get is confirmation that hammer time was overkill.
9. The code found in the lab was the date of the first dating game, with an extra 27 at the end. What is the meaning of the 27? It's probably a reference to Simon and E having the numbers 2 and 7 on their collars, because Emily loves clues that no-one could possibly figure out without already knowing the answer.
10.What happened in ending P? H has a stab wound in her chest, and her collar took off her head. The fact that she was in the station means it shouldn't be from entering a room with too many people.The other rule we know is no trying to remove the collar. In ending R we saw that a well placed stab can shut down an EMILY's ability to move while leaving them alive for a while, which would make it easy for the attacker to take the collar triggering a beheading in the process. But the stab wound is also weird. The attacker taking her knife implies they didn't already have a stabbing weapon. It would make sense for the attacker to shoot H, take her knife for stealth and/or ammo preservation reasons, and grab the collar while she can't move. But Simon calls it a stab wound, not a gunshot. Is Simon just bad at autopsies? Did the attacker wrestle the knife from H rather than risk making noise? H was counting on her superior robot strength, but everyone is secretly a robot. Using the knife on Agnos and the gun on E feels strategically backwards, which might suggest that the attacker needed to kill Agnos to get the gun, which would mean not having the gun yet when taking the knife. Next, there is the question of who the attacker is. Simon uses process of elimination to say it must be Marco or Ray, but the reactor was closed earlier and we know that it is a dead end. Did the survivor grab the collar from the remains and go on a killing spree instead of trying to leave? Did J/Greta turn around from their attempt to leave and go on a killing spree? Emily said she set it up so only Simon and/or E could leave, but never specified what this entails. Do they get hijacked into doing something like ending G?
11. Did Agnos deliberately disable Marco with coconut? Agnos responded to Marcos one line before he talked about his severe allergy, so it is plausible that that part was overheard too (however, this discussion is optional). He also is always able to figure out that Simon likes lime, and he instantly guessed that the allergic reaction is to the coconut rather than something else in the drink. Later in that route Simon thought Agnos was trying to keep him from Marcos which never got explained. Agnos could possibly know of Marcos from his role in the Empty S, and with that route having rising paranoia decide to interrogate him. It also gives Agnos an excuse to head to the infirmary, which he almost always explores and finds the remote he obsesses over. It is unclear if he is making choices with inside info (similarities to NY?).
12. In ending A, after hitting the zero button doesn't work they try -2 next. Simon then goes out and sees a scanner room. But aren't the even-numbered rooms the stations below the active search areas, with -2 being below the theater? There shouldn't be a scanner there.
13. For that matter, based on the map of the "Oval Tree" and the combined floor map shown after J realizes what it is, there should be four elevator shafts. Does that mean that each elevator can only access 3-4 of the AS rooms, or is it less evenly distributed? Ending A does have some unspecified button presses not work before even trying the zero button, and other uses of the elevator don't even try going to the AS floors. Yet when realizing how the station is layered, Simon thinks that the single elevator means there is a single exit and only one pair can escape. (Of course even if it were a single shaft that shouldn't be a problem, judging by Ending Q, but I'm confused as to the number of shafts.)
14. Does Greta know that H is a robot? At multiple points Simon wonders if she is covering for her sister, and I can certainly see her comments about the note making sense in terms of "I know my sister was replaced by a robot, but love her anyways and don't want her burned at a stake", but her reaction when J and Ray call the late H an imposter seems genuine, and at the reactor H claims Greta doesn't know. For that matter, does H know? She says that deep down she always knew she wasn't the real Hannah (and this fits with how she jumps to the conclusion that the note is about an imposter), but that isn't necessarily the same as knowing she isn't human. At the reactor her comments about the first law suggest she didn't know she is a robot until the recent memory dump. On the other hand, in the orange route Simon thinks she may be only pretending to struggle against Ray. This could make sense if she is trying not to prove his accusations correct by demonstrating robot super strength. (I was going to go on a tangent about the twins being the ones to explore the security room in the light green route, but after thinking about the timeline more that theory didn't help explain the competing evidence at all).
15. In the reactor, after the sacrifice Smiley says "However, know that, now, someone else has been condemned to die here." What does he mean? The obvious answer would be that Agnos can't possibly escape with H's collar in here, but that wouldn't hold if the right people paired up and Smiley explicitly acknowledges that possibility later in the same speech.
16. In ending A, Simon isn't sure whether his favorite color is blue or green. What's up with that? In the blue route, he is decisively states that green is his favorite color.
17. In the blue route, where did the key come from? In the pool, J says she has no clue where E could have found it. Then in ending J, J claims E found it in the infirmary. But last we saw E (pAStime2), she was only just leaving to go to the infirmary. Was the key actually somewhere in the lab, which J and E explored together? Did J and E clear two rooms and still make it back before Marco and Ray turned around, which she then keeps secret? Was it actually hidden in the pool, which J had a few minutes to search alone, and then she lied about getting it from E? Were the events of pAStime only valid for routes E/F, with J/P having different outings that got hidden by the collar reusing the old memories (like the pink route)? In the last part of the light green route (A/B/S) Agnos seems to be able to use the station elevators, but that doesn't help narrow things down since almost all stations were searched and Agnos could possibly have looted it off any of the corpses. In ending I Greta seems to come from the station elevator, but her last location is unknown and Simon's knowledge of her location before that is possibly false, plus there is Agnos's dead body to loot, so this doesn't narrow things down either. In ending N Agnos shows off the key, but doesn't say where he found it and his location history is unclear due to lying. (For added uncertainty, it is not like it was ever confirmed that the theater key or even the library key cannot be used in the same way, adding more possible explanations in A/B/S and I.)
18. In ending H, what's with the rubble? Agnos is dead, so he can't have gone on a bombing spree. There was no mention of "earthquakes" either.