I have noticed that you can choose between Normal and Hard at the start of a run in The Binding of Isaac: Rebirth. What changes when you choose Hard?
As mentioned here by Ed, some effects are no heart drops from bosses and curses being more prevalent.
I'd hazard to guess that less drops in general and higher HP enemies might play a part. Especially less drops.
And here's his general notes copied over from the linked post:
- Beating different goals in Hard mode will unlock new content not unlockable on Normal.
- Beating said goals in Hard mode will also unlock any unlocks that would be gained by beating Normal mode (so you can start on hard if you’d like)
- There will be achievements for Hard mode.
- Hard mode will have some visual hud/menu changes so you are always aware if you are playing on Hard. (or watching someone play on Hard)