I want dark, mean, soul-crushing realism in a fantastic game that takes me to faraway nonexistant places.
I also want it to be extremely violent, real-time with light RPG mechanics and a fast-paced combo-based combat system, have crushing difficulty yet lets you attain stunning power both by gameplay and story standards by the time it ends.
Oh, and multiplayer. And a 50+ hour plot with memorable characters that will make Alyx Vance look like a blow-up doll by comparison.
And while I'm at it, I'd like a million bucks, a jetpack and a pony.
Seriously though, I have little preference but I generally prefer a game that is realistic to one that is pure fantasy when it comes to what you can or cannot survive. (IE: If you get hit in the head by a chainsaw, you will not go "ow, 159 damage!". You will go "OH HOLY MOTHER OF-" followed by wet, sputtery-splatty noises. But if you MUST do the 159 damage thing, keep it internally consistant I'M LOOKING AT YOU FINAL FANTASY SEVEN!)