Calvin & Hobbes
The Far Side / Bloom County
I've read a LOT of comics, including every last panel of all those named above.* Nothing ever approached the brilliance, humor and art (in combination) of Calvin & Hobbes. I had a really difficult time deciding whether Bloom County or The Far Side should be in second place, so they're grouped as a tie in my mind. Dilbert fluctuates between average and absolutely brilliant.
Respect to Peanuts, which was my first favorite as a child, but it never achieved the heights that the others mentioned above did.
All IMO, obviously.
* I may not have read every last panel of Peanuts; it's impossible to know.