If there can be only one, best of the bunch, for me it'd be this:
Left 4 Dead
No other game could turn our group of casual players into such a well honed machine of zombie killing survivalist commandos like this one did. Our bond was almost psychic, with each of us helping to develop our group survival instincts for every situation, whether one of us was blinded and set upon by the horde, to timing the perfect pipe bomb throw, to shifting into formations and firing in teams so that there was always one group of two firing while the other two reloaded. If I had to pick just one game this gen that epitomizes modern multiplayer for me, it'd be Left 4 Dead.
Runner ups:
Gears of War 2 : Horde Mode
The best
defend against waves of enemies mode of them all. The ground shakes from the footfalls of giant locust and explosive ordinance, heads crack, shields get battered and topple, and eventually all is lost, and everybody dies in a tatter of pulpy flesh. Unless you can make it through wave 50 that is.
Halo Reach : Firefight
Horde, but with a wider sandbox to play in, a fuckton of customization options, and the addiction that comes with gaining cR to spend on armor doodads.
Modern Warfare 2 : Spec Ops
The main reason I miss Infinity Ward, and the only reason I would consider rejoining the fold of COD. Two players, tons of variety, tons of mayhem.
Borderlands
Phat loots, satisfying combat, tons of stats, challenges and questlines, humor and madness, all tailored for co-op? Sign me up.
Grand Theft Auto 4 : Mafia Work
Get some beers, some buddies and boot up a session of Mafia Work. If you don't end up with a ton of crazy stories that rival the best action movies, you're doing it wrong.