Any of the fucking HALO games. I personally never really got the Super-Smash-Bros games so I'll put them up there too. MGS4 is a cert. WOW for obvious reasons, (I say that as a non-WOW player, I just hate the damn thing.) Eve Online I to the the whole online experience was very disapointed with, I muched prefered Freelancer for that particular genre. Saying that, I'm not really into the whole 'Online Experience' so maybe I'm just a hermit.
However, none of them hold a candle to how much Resident Evil 5 shat itself all over my living room floor.