Arguably two of the most popular American cartoons that are aimed at an older age group, The Simpson's and Southpark have always put up good ratings... the question is which one will go longer?
My reasoning is Southpark, as much as I hate to say it, because the Simpsons is getting worse every year, and eventually they will run out of concepts. If people don't get sick of the crude low humor, than it will stay because new issues and groups to insult will always arise.