Left 4 Dead is great multiplayer fun.
Dead Rising, just for those days when you gotta bash some zombie heads (with flower pots, bowling balls, baseball bats, frisbees, soccer balls, benches, marqui signs, yeah...).
GTA4 is good, too. It breaks from the, "oh, I'm a gang banger, look how hard I am," BS that was San Andreas. Huge area to explore, lots of stuff to do to kill time.
As others mentioned, Oblivion, Fallout 3, Gears of War series, Assassin's Creed.
Armored Core: For Answer is a blast, if you like blowing up giant mecha in a giant mecha.
Level me up! I, too, wish to storm the lands of mortals reaping what is truly mine...but for now, I am but a wee spot of energy...
"I embrace death without fear as I embrace life without regret."