Editor's Choice: World of Warcraft (Blizzard Entertainment)
It's hard to argue against WoW. Its subscriber numbers are not even comparable to the competition and its penetrated pop-culture in a way no other online game has ever dreamed of. From South Park to the nightly news, World of Warcraft is a worldwide phenomenon and only continued to grow over the last year.
So many people have tried WoW that it would be insane to expect them all to like it. Veteran MMO players sometimes consider the gameplay experience derivative and many are weary of the end-game's repetitive raids. Nonetheless, it's revolutionized the genre and undeniably had a major influence (or perhaps counter-influence) on every game that followed it. For that reason, World of Warcraft is easily the Game of the Year in 2006.
Honorable Mention: Guild Wars (ArenaNet/NCSoft)
Honorable Mention: EVE Online (CCP Games)
Both EVE and Guild Wars made huge strides this year. Guild Wars may have fundamentally altered the way people consider paying for these games, and EVE continued to grow like a weed; so much so that their parent company merged with pen-and-paper giants White Wolf. In a different time and place, either would have been worthy winners.