This is more like "the games I've enjoyed the most" as opposed to the best, but:
Civ IV (with expansions) - I think Civ V is objectively a better game, but the sheer amount of time and effort I sunk into Civ IV is mindboggling.
Knights of the Old Republic - The second game had better ideas, but this one was just about perfectly structured, super fun, and no, I did not see the plot twist coming. I don't even like Star Wars; I think the games took the best Star Wars concepts and did something interesting with them.
Portal - I like Portal for the same reasons everyone else likes Portal, I guess.
Planescape: Torment - Besides the great story and characters, they also did an amazing job of integrating the game's concepts with the RPG setup
Assassin's Creed 2 - Again, I appreciated the clever integration of story with the game interface. The game was just plain fun to play, and the story and characters were more interesting than the first one in the series.
Super Mario 3 - If you were alive and playing video games at the time Mario 3 came out and you don't love it, I don't even know what to say to you.
Myst - I have no idea how well this would hold up if I played it now, but I have such fond memories of sitting with a friend at the computer, clicking through the environments with bated breath. Also, it was the first game I played that had a substantial plot.
Red Dead Redemption - The Grand Theft Horse gameplay is a blast, and the endgame felt like a punch in the gut, but in an Oscar bait way instead of a ME3 way.
Mass Effect - speaking of ME, goodness, I loved the first game. I enjoyed the other games, but the first game (despite some flaws) had such a great balance between the shooter mechanics, the RPG elements, and the action-adventure storytelling, and the game universe felt like a fresh take on some big sci-fi concepts.
Super Smash Bros - SSB + a group of friends + booze = hilarity
The Legend of Zelda: Wind Waker - the design style and tone of the game are charming. I spent forever sailing that boat around.
