South Park. Why? Because the entire show is a juggernaut. Not a single chink in its armor. The Simpsons relies almost entirely upon Homer to be worth a damn anymore. If they killed him off, the show would die. South Park could lose just about any character and suffer minimal damage. The loss of Cartman would cause the most damage, but the show would still be great.

Plus, South Park relies upon current events for it's humor, therefore providing an endless stream of material. The Simpsons relies on the weirdness of the writing staff to come up with new wacky situations for Homer to get caught in every week. A human being can only crank out so much oddity before the well runs dry.