Adding more things that can be different between runs could be nice, cause the replayability is a bit lacking for a roguelike. Things like alt-floors or just alternative enemies, different sets of starting babies instead of always starting with the same few (maybe have the different characters from Isaac with different starting babies each?), and maybe some variance to the boss fights, like different arenas or attack patterns. Basically just more stuff that you'll see in one run that you might not see in another, especially in the early game