There was a Playstation southpark game. It kinda sucked ass - like rather than make a funny or enjoyable game, they made a turkey fest of a travesty of a first person shooter.
You had to throw snowballs at turkey's, millions of turkeys, and your pals if you wanted to play split screen. Really nasty little game that probably made them a fortune.
A southpark game might be a nice idea if you can keep that southpark look - the old paper cut out style should be easy enough to emulate - if your planning on going 3D then I suggest you simply forget it, a 3D southpark game is a complete cop out. You could use simple plains like cut out pieces of paper, textured to show face animations. It would be very easy to make 3D models, throw in a cartoon shader, but that's been done and didn't go down too well.
Maybe more of an adventure game would be an idea - like maybe the boys need to raise money to buy the latest videogame console, so you could have them do chores for popular residents of southpark.
P.S. If you use Cheesy Poofs as energy replenishers I will come to your house and cut you
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