Haha, funny that you mention an Edmund McMillen game... I actually live in the same town he does, and one of our close family friends lives just two doors down from him and his wife, so I've been able to discuss game-development related topics with him on several occasions.
He's definitely an interesting character, I'll give him that. ^_^
Anyway, yeah, I actually own Binding of Isaac on Steam, and while it's definitely a wonderful game in and of itself, something about modern roguelikes (as in basically everything after Nethack) just doesn't keep me interested when playing. I'm pretty sure it's because I like a game with a fair amount of "depth", either in the form of story, or gameplay features (as in the "in-depth" mechanics of RPG games).
Additionally, while some roguelikes often DO, in fact, have the features mentioned above, just the fact that you have to start over after you die gets to me. I'm the kind of gamer that tends to want to do everything in one, single playthrough, which therefore means that I don't often get much replay value out of games (aside from the strategy genre). I'm fairly sure that it's those reasons that I have an issue with roguelikes, as once I die, I
loathe having to start all over again...
...which is probably why I was an AI developer in the game industry, and
not on the side of development that created gameplay mechanics or overall design.
P.S. - To relate to both the Edmund McMillen AND roguelike topics, Super Meat Boy was very enjoyable for me (unlike some other platformers), simply due to because when you died, you did NOT have to start the game over from the beginning; just the level itself.
P.P.S - Also, while many of the adventure games of yesteryear had a roguelike feel to them (do something wrong or fall in a hole, and you have to start over from the beginning), I have no problem whatsoever playing them. This is because the story *completely* distracts me from the fact that I just

ed up, and have to play again from the start...