I love this game to death (this account was made JUST to leave suggestions to your game), meaning I have a lot of problems with it, because I want it to be perfect (impossible)
To make this easier to read i'm just going to post my two main ones, Boss battles are lame, the first 3-ish levels are boring.
For boss battles, It's kinda lame how I can't select babies, but dealing with recharge in a boss when they can just instant kill 3 lanes sounds bs, my proposal, make the bosses instant kill moves (plum gun, ragdoll skull, middle horn laser) only happen once or twice at specific health values (1/2 1/3, whatever) and/or make babies recharge and hearts fall both twice as fast in boss battles. You can even make this only apply in hard mode, that would make me play it a LOT more (personal preference, hard mode is fine.)
For the starting a run issue, it's already super fast so it's not a big issue, it's more of a personal thing. Maybe after beating hard mode, you can select from a starting deck, with a unique upside and downside to choose from for each one. Basically, after beating hard mode you unlock characters to choose from, and after winning a run (hard/normal/both, idk) with one of those characters you get an achievement with like, isaac baby, maggy baby, cain baby. Legit I would spend so much time playing a lost character that can't get heart producers, but babies and actives charge twice as fast. You could add the worst fucking thing imaginable, and I'd play the game for a month without giving up.
TL;DR, I would like to select babies before a boss battle, because random babies are kinda lame. Different ways to start a game by selecting prebuilt starting deck with some kind of drawback and upside would add a lot of replay value, especially if winning with a deck gave an unlock.