After playing Binding of Isaac for countless hours, I have to say I really enjoy it. Edmund McMillen never runs short on his imagination. However, I can't help but feel that it could use a multiplayer option, particularly if there ever happens to be Playstation 3 and Xbox 360 versions of it.
Here's the ideas:
1. Multiplayer modes: These could range from typical deathmatchs where players try to kill each other in various dungeons as well as coin battles where everyone tries to get the most coins. There could even be a mode where you can only harm other players with a brimstone power-up that you and the other players try to reach for.
2.Co-op: Basically, you and another player have an attempted story mode run. Since you have a second player, assistant upgrades such as Meat Boy and Rainbow Baby would have to be disabled. Also, both players would have to exit a room at the same time to move on.