One of the things I have never liked about Foxtrot are the constant pop culture references. Bill Amend is mailing it in, which is his right, but I don't have to enjoy it.
Runners-up: Brewster Rockit: Space Guy!, Daddy's Home, Dennis the Menace, Garfield, Hagar the Horrible, Rhymes with Orange, Speed Bump
Here we have the rare joke that is both literate and well-crafted.
Runners-up: Agnes, Cul de Sac, Dilbert, Family Circus, Get Fuzzy, Mutts, Non Sequiter, Pearls Before Swine, Prickly City, Single and Looking,