I reckon this thread needs a giant bump.
The great thing about the simpsons is that it can be watched on so many intellectual levels...a ten-year old and an English teacher with a masters degree can both watch it and enjoy it the same. I pretty much grew up on The Simpsons, and I still watch the old episodes on a daily basis, and quote them everytime I get the chance. I love the Simpsons characters far more than any other cartoon (besides maybe a few Futurama characters or Harvey Birdman characters), especially the secondary characters (i.e. Lionel Hutz; "Well, he's kind of had it in for me, since I accidently ran over his dog. Actually, replace `accidently' with `repeatedly', and replace `dog' with `son'."). If anyone still needs to watch the old episodes at anytime,
http://www.iwatchsimpsonsonline.com/
I like South Park because it satires current issues/news stories/movies/etc..the Economy episode had me laughing throughout the entire episode. I put it at second.
I'm not even going to put Family Guy on this list, I really hate Family Guy. Maybe it's because I don't get most of their pop culture references. But I also hate it for the fillers, which seem to be more than half the show. I will admit, when I do watch it, I like Brian.
Futurama should be on this list. I would put it ahead of South Park. Zapp Branigan is one of my favourite cartoon characters ever. The stories are great, and the movies don't bomb like most other cartoon shows.
Harvey Birdman: Attorney At Law is fucking hilarious. Everyone should look it up. If you enjoy randomness to the max, this show is perfect for you.