moderate-major spoilers
I realized that part of why I was getting my ass kicked so often is because I had been amassing a hoard of stat ups and forgetting to use them or putting it off. I used them, got the level-down potion from the illusory bartender, and opted in at the shrine all in short order and things seem to be a touch easier. Nobody even died during the room 2406 quest although I imagine that was balanced to accommodate a possible 2-character party. It was refreshing to be able to deal with things like the Double Wrath Slime and the Prankster Rat King where before they were inescapable game-overs. A hard mode in which the pills have a 0% chance to drop could be an option for masochists, though I can't speak to how mathematically doable that would be, past the rank-1 missions.
On the shrine: I visited the church after - I don't know if that "traded off" the big stat up and I didn't do a before/after comparison to check. The creepy statuses in combat went away though. I didn't keep it around long enough to see if it was going anywhere, I figured anything with that much foreshadowing had a good chance of getting me killed and with my newfound stat-boosted overconfidence I didn't want to leave that risk on the table while save rationing.
Some little issues I ran into:
Couple of lines where Ramona's dialogue starts with "Ramona>" and Kyrie's with "Kyrie>" in the downtown sewer Faunshalt Family conversation.
In Patrick's bounty office there's a bounty on the Butcher. When you read it, there's no opt in or out prompt and you automatically lose $50 and get a complimentary hint token. The dialogue (and trade) was totally repeatable, I don't think I signed up for anything.I also killed the rat guy before even meeting Patrick so when it prompted me to go see him I was despairing that I had forgotten an NPC's name.