Red Dead Redemption is my favorite game ever, so it's not even close for me. I have played through the story mode multiple times and have yet to get bored, and I've spent hours on end playing online multiplayer. I cannot sing this game's praises enough, but I will try.
First of all, what could be better than a game set in the Wild West? Cowboys riding around, shooting guns at outlaws, exploring the wilderness (which is composed of the most beautiful scenery you'll ever see in a video game as far as I'm concerned). The concept of the game was spectacular to begin with, and they executed it perfectly. The guns fire like you'd suspect a gun in the late 1800s to fire. The combat characteristics are also great, as you have a realistic cover system that isn't broken like the cover system in GTA4.
The missions were fantastic, straight out of Spaghetti Westerns. You chase after a moving train, bust into a fort full of outlaws armed to the teeth, you race around the desert with a bunch of homicidal maniacs... it's like you're acting out all the traditional Wild West moments in a video game.
When you're not doing the missions, you can hunt, do sharp shooting contests, try your like at cards or dice, duel, or just explore the landscape and encounter all sorts of new and interesting people.
Red Dead Redemption is a perfect game in my book, and it definitely deserves to win this match up.