That's difficult, but...most likely two games- Sonic 3 & Knuckles, which basically was my entire childhood, and I still play it at least once a year now- I lost count of how many times I finished it a very long time ago. I could practically draw the level layouts from memory.
The other one is that Zelda game. You know the one. With the Wind, and Waking it and everything? Wind Waker I think? That one. I've played Wind Waker start to finish about fifteen or so times, and that isn't including all the time I just spent screwing around in it, like seeing all the inventive ways I could knock Bokoblins off of ocean platforms.
The multiplayer game I've played most is good old Super Smash Bros. Melee, as I would play it at least once a week with my friends from 2002 to 2005, and holidays were spent playing it and other games non-stop with said friends.
However, for an actual statistic like which game I've spent the most hours playing, I really don't know.