When I was growing up my favorite comic was Far Side, followed by Calvin & Hobbes, Bloom County/Outland, and Fox Trot (in that order). All of them had the perfect blend of awkward social situations, nerdiness, and (with the exception of Fox Trot) complex questions made digestible by self-aware animals.
Not that I read a ton of comics, but those are still my all-time favorites... and aside from some funny stuff like xkcd and Bob the Angry Flower, I haven't really found anything that could rise to that level. Garfield minus Garfield definitely fits, but aside from the concept (which really is the funny part of the whole series), it is hardly an original piece of work. A trending topic in Reddit this morning was the question of how many people under 30 knew (and loved) Far Side. That in itself is an interesting question. Comics which pre-dated my childhood, such as Archie and Peanuts, were still around when I was growing up - but those are comics that I still see in reprint today, unlike Far Side and Calvin & Hobbes (which I'm more likely to see resurrected in a powerpoint presentation). Anyways, discussed in the Reddit thread was one of Gary Larsen's contemporaries & influences - B. Kliban, who was a cartoonist for Playboy and created the Cats cartoon which were on all the Hawaiian Crazy Shirts back in the day. Apparently Kliban invented the 1 panel comic which people like Gary Larsen and Jim Unger (Herman) made famous. I looked up some of Kliban's shit - pretty impressive. I'm going to stick it in my humor section.