Disney's ToonTown Online. I think I put over 1000 hours into that game. After that, it would definitely be RuneScape, unless I'm underestimating the amount of time I put into the same couple of video games as a kid. After that, it is very hard to say.
For this generation of systems, I put over 225 hours in Demon's Souls, which is my favorite game of all time. LittleBigPlanet, LittleBigPlanet 2, Uncharted 2: Among Thieves, Super Smash Bros. Brawl also garnered a lot of time from me, but it's hard to say how much. I'd say I put in at least 100 hours into each game, except for LittleBigPlanet 2 maybe, seeing as it is fairly new. As for the rest of the generation, I really don't think I've clocked any other games over the 100 hour mark.