Everything Parker and Stone have done after South Park has been very successful. Both the South Park movie and Team America were critical and commercial successes. Book of Mormon is also the big thing on Broadway right now. It won a bucket load of Tonys.
Also, South Park has included well done satire on occasion, and isn't just about pushing back the boundaries of inappropriate content. I'm not a big fan of the show, but making a South Park RPG isn't some sort of terrible selling out of Obsidian's high brow role playing pedigree. Alpha Protocol was filled with lewd humour, for example.
Besides, CRPGs and their fans have always taken themselves way too seriously and are really asking for some proper satire of the genre. Personally, I hope Obsidian and the two guys include cosplayers, conventions, larpers, fanboys and overly intelectual RPGers as targets for their humour.