Though Ctrl+Alt+Del was never lacking in detractors, it was probably the second biggest gaming webcomic of its heyday (next to, of course, Penny Arcade). Sometime around 2008, though, the infamousmiscarriage arc, the utter failure of the Animated Adaptation, and the antics of writer Tim Buckley caused the comic's fanbase to collapse. The comic still survives in a heavily-rebooted form, but it now struggles to maintain readers, and the only time it comes up in most discussion is when taking the piss out of it. Plenty of people aren't even aware it still exists.
Chugworth Academy was huge for a time, with its Animesque art pleasing to the eye and the great deal of fanservice and quick gags making it pretty popular. However, Schedule Slip, and the creator Dave Cheung's seedy reputation (and penchant for drawing pornographic and guro comics) led to it being not even a footnote in history. Nowadays the fact that he drew pornographic and guro comics overshadows everything else he has done for lots of people. To the point that most parental advisory sites say that everything he has ever done is not safe for work.
Megatokyo may be the webcomic world's counterpart to Inuyasha mentioned on the anime and manga page. It was the premier webcomic in its golden age. It was one of the first webcomics to be adapted into a graphic novel format. It used to draw bigger crowds than Penny Arcade at cons. The forums were one of the largest English language internet hangouts outside of Usenet at the time. If you read webcomics in the early 2000s, chances are you either read it, know about it, or read a webcomic whose author was inspired by it —that's how big it was. Then it all collapsed. Readers started to realize that the overly complex plot was going nowhere, not helped by its Schedule Slip going into overdrivenote a pretty impressive feat considering that even at its peak the comic was infamous for this thanks to growing problems with Gallagher's real life. The distinctly rough Animesque artstyle that attracted people in droves repelled just as much as the medium expanded and more webcomics came into play with much more polished art. Tack on the frequent use of leetspeak (which almost nobody seriously uses nowadays), Megatokyo transformed from a contemporary comic into an Unintentional Period Piece. Much like CtrlAltDel above, many people nowadays are surprised it hasn't completed its story.