Top spot goes to The Legend of Zelda: Ocarina of Time, easily. I beat it close to thirty times when the N64 was in its prime, and I still occasionally go back to it. I've got to have clocked close to 1,000 hours there. Don't regret any of it: no other game can elicit the feelings that OoT does. Best thing ever.
Second place would probably be to Final Fantasy X. If I had to guess, I would say that I put near 500 hours into it. All of my playthroughs clocked in at around 90 hours, and I beat it about five times, so you do the math. If I still had a PS2 (or my PS3 had backwards compatibility...), it would be more. If the HD remake ever sees the light of day, playtime there will definitely skyrocket.
Rounding out the top three would probably have to be World of Warcraft. I haven't played in months, but I'm pretty sure I would have clocked in around 200 hours total, on all characters. I didn't play it much, but when I did play it, I played it for long stretches of time. I'm actually kind of glad I got out, because I do regret that time spent a little bit. And the money...
Honourable mentions other than that would have to go to The Elder Scrolls IV: Oblivion, Super Mario World, Dragon Age: Origins, and Demon's Souls. So many fond memories.