I think it's so subjective that I couldn't really say who I think is the most successful. Is it about financial success, or about how dedicated your fans are? Is it about how widely you're read or whether you've cracked the mainstream? Is it about having your strip adapted into an ADHD show? Is it about print syndication? Is it about making your readers laugh, or cry?
I'd say Penny Arcade, xkcd, The Perry Bible Fellowship, SMBC and Axe Cop are the webcomics that come to mind when I think 'successful', but all for different reasons.
I think PA have definitely cracked turning a webcomic into a moneymaking behemoth, with all the merch, web shows, conventions etc. But xkcd has become just as popular, if not more so, on little more than the merit of the strip alone, which I think is more admirable. It helps that its content is a lot more accessible, I guess - you see xkcd referenced and reproduced in the mainstream now - but I definitely think the actual strip is more consistently well-written, too.
Zach Weinersmith's the only person I can think of who makes a good strip every single day. TPBF has hands-down the best jokes I've ever read, and Axe Cop is a genius idea. Those are all successes too, for me.