That's actually a tough question, and to be honest, I was thinking about it for a while. However, I start to realize that no video game can actually fulfill that requirement (or at least not "mainstream game"), as they aren't updated regularly, and after a while, you'd get bored of it. Lifespan is actually too long for one game, doesn't matter how good it is.
If I can "cheat", I'd say one of the Skylanders games, as because of how they work (regular updates via figures), they actually take more gameplay time than any other games currently. Or I'd say an online game like Elder Scrolls Online (for me, it is still considered "cheating")
If I can say games other than video games, I'd say Cardfight!! Vanguard. It is just the perfect trading card game for me. All the clans featured in the game are completely different worlds with different art, design, and completely different playstyles. To make it even better, the regular "updates" (new expansions/boosters) are actually supporting old cards.
If I can only say a non-online video game, I'd say one of the LittleBigPlanet games, or Journey. If it is the "imagine you're on an island alone" situation, I'd definitely go with Journey. Not only it has a deep meaning and perfectly defined as a form of art, but in such a situation, it'd help me keeping hope in myself.