This is a hard one, because on one hand it'd be so easy to pick something like Super Mario Kart, Street Fighter II, Quake 1 or Mario 64, all of which defined my childhood, but if I'm honest with myself ...
It's World of Warcraft.
I've played it on and off since release and I fully intend to play it again. I've always enjoyed it and now that Titan (Blizzard's next big MMO) got cancelled, I'm convinced the genre is dying out and WoW will simply never be matched.