If you don't like Calvin and Hobbes you're not human!
Matt Groening's "Life in Hell" is another great one.
Technically this isn't a webcomic, but it's still pretty damn funny.
Who would have guessed that when you remove Garfield from the Garfield comic strips, the result is an even better comic about schizophrenia, bipolar disorder, and the empty desperation of modern life? Friends, meet Jon Arbuckle. Let’s laugh and learn with him on a journey deep into the tortured mind of an isolated young everyman as he fights a losing battle against loneliness in a quiet American suburb.
http://garfieldminusgarfield.tumblr.com/