i think south park is awesome
futurama was awesome
simpsons is the least of my faves now (but there's no denying how great it's been)
King of the hill is the most minimal and also has the most heart.
family guy is great for a good laugh.
South Park all the way for me. The film was incredibly funny and an unexpected Disney like Musical with a tourrette's syndrome cursing streak. The show whenever it got topical, had a hilariously skewered take on the situation and flipped the bird at whomever they pleased.
Family Guy works for me second best because of their Airplane! like tactics: throw everything you have at the wall and see what sticks. Their political incorrectness rivals South Park, and that's saying a lot for a network broadcasted television show.
South Park is the only modern musical in my memory that had people signing along in the theatre. The utter brilliance of the extended songs and dance numbers is really hard to find a comparison to. Even without the 10 years of episodes I could call it the greatest based on the movie alone.
Futurama is the most verstile of the group and is the least restricted by reality. At the end of the day if Futurama wants an episode where bill clinton dukes it out with george washington while captain kirk rates the fight all taking place on a planet where gravity is constantly changing they can do it. If futurama wants a war they have a war if they want 1920's they've got it.
Id say of the group its probably my favorite. Although the Simpsons changed the world and our culture after the Johnny Cash space cyote episode it really felt like it went down hill pretty quick. I'd have put the Simpsons first if they had killed it 5 years ago but the last 5 years really dropped the average for me. Of them its likely the most significant and important but for me its running third.
South Park and Futurama are unique in that many people never watched them on Television. I watched both series while at work having downloaded them each week as they came out. I have owned both series in a pirated form more than once.