I have to agree about family guy there. Personally I have very little interest and/or knowledge about celebrities and celebrity culture, especially people that were famous from before my time. A lot of Family Guy's humour comes from making reference to these people, which I therefore just don't get. It's not really the fault of the show as much as it is mine, but I feel like one episode they will make the humour really accessible to everyone and then the next episode only people 40 years old+ will get. I tried to watch it back to back at one point but it really didn't hold my interest very long.
My friends and I have always been South Park fans. Despite some over the top crass humour a lot of the time that won't be everyone's cup of tea, a lot of their episode concepts are really good ideas. And a lot of the show's humour comes from it's parody approach to real life situations - which to me is a lot more relatable than Family Guy.
Also the fact that I am Ginger, Jewish and half Canadian just makes watching it a very humorous irony for me. I learned a long time ago that a lot of great humour comes from learning to laugh at yourself, and with my friends and I, we saw so much of ourselves and our interactions emulated in SP that we just found it so much funnier.