I genuinely consider SMBC to be a work of genius. It's sometimes incredibly profound, amazingly moving, truly original, and almost always funny. And, miracle of miracle, with over 4000 comics done, there's been no drop in quality. Indeed, almost all my favourites come from the latter half. Basically, it's everything that XKCD is, except more consistent, more prolific, less esoteric and, in my opinion at least, just better. It's certainly no less intelligent. Don't get me wrong, XKCD has done some brilliant and massively inventive comics, but... they're spread thin over the years.
Other webcomics I have bookmarked are Oglaf, Penny Arcade (although they've truly disappeared up their own arses over the last decade) and Deathbulge.