It's hard to narrow down to just one, but if I had to it'd likely be Unreal Tournament. I don't think there's a game in existence I've spent more time with, except possibly the original SMB. It's wonderful out of the box, and mods like oWo's TallyHo! (if you can even find it anymore), the little smiley-faced grenades, and the range of sniper/camper stuff out there only expanded on that wonderfulness. It's also one of the easier games out there to mod; as lazy as I am, even I have made a few things.
I'm also going to say Pac-Man, crushing my dreams of a list of one, but I think it's worth it. Here lately I've been losing hours to Pac-Man CE, a fantastic iteration up from the original game.
And I'll end the list with Mario 64. I still think it's the best 3d platformer to date.
Minecraft has the potential to make the list, but it'll have to work out some kinks (read: no longer be in alpha) first.
This thread made me register. Just sayin.