Gotta give a shout out to Mass Effect.  Got it for Christmas from my wife, just finished it, and it's one of the very few single-player games I immediately started through for another run.

It's not perfect by any means but it is one hell of a story.  One of the sidequests, basically just a conversation, that you can run across is one of the most heart-wrenching things I've seen in a game, and given my cynicism, that takes a lot.