Real Life Comics suffered from a form of Creator Breakdown twice, both times when Greg Dean broke up with his then-current girlfriends. Rather than affect the quality of the series, though, he simply took a brief hiatus from the comic (as he didn't feel like working on it at the time) and returned a week or so later and picked up where he left off, with the ex-girlfriend's character vanishing without a trace and never mentioned again. Of course, Greg has since gotten married, so these mini-breakdowns may be a thing of the past.
One strip does playfully lampshade it, however; Greg and Tony are visiting multiple dimensions and they stumble across the Offstage Waiting Room where Crystal (the first ex-girlfriend) is playing cards with Danny (a friend who gradually faded out of the strip). Crystal looks up and says, "What, did the Artist get bored with you, too?"
In 2002, Ubersoft.net took two-and-a-half months out from an ongoing plotline to inflict the author's computer woes on one of the main characters.
A similar story is behind the Bob the Angry Flower strip My Computer Is A Monster, in which Bob's computer unplugs itself, grows to the size of a small house and rampages through the streets eating people.
While the official explanation for why RPG World was canceled is due to Artist Disillusionment, the fact that the main arc just suddenly ended without any noticeable decline in quality during the ostensible final storyline, along with a couple post-script side stories that basically curb-stomped the characters, seems less like actual burnout and more like some event really turned the author against his work.
With Act 5 over, Act 6 seems to have hit a reset button on everyone's pent up emotions. Ironically in hindsight it seems that while Hussie was fine, the fans degenerated into angry fitiful infighting and constant drama.
Parodied in a brief Bob and George storyline, in which the author character becomes extremely depressed, causing the strip to literally start to fall apart, with panels sliding off each other, becoming disoriented, and appearances by characters who are supposed to be elsewhere. Naturally, the problem is solved with explosives.
Doobl was a short-lived comic that started as a Christian evangelical comic and became eventually more and more dark when the author's mother died, finishing in killing off every character and then the author himself. It was later made official that it was a Stealth Parody, but man, it'd be easy to get fooled.
Anne Onymous, pseudonymous creator of The Wotch took a hiatus when her marriage abruptly ended but came back and soldiered on for nearly a year before petering out again without much explanation, citing unspecified "avoidance issues."
Brawl in the Family creator Matthew Taranto suffered a short case of Creator Breakdown when his Wii was gutted out and lost all of its data. He drew a bonus strip where all of the major cast members as well as the Earth itself were destroyed by the Sun, as a comedic reference to a previous bonus comic.
Not to mention he is currently struggling through literal breakdown with horrific illness, and is in too much pain to update the comic, though he wishes to.
Things are looking up, though. He is recovering from his illness and is now well enough to continue updating the comic.
The webcomic Avalon unfortunately suffered from this more and more as the author went through progressively worse states of depression not long after being launched. The planned four-year series lasted much longer due to month-long hiatuses. After a year of not-updating, the author gave up and the ending was written out instead of drawn.
Living with Insanity was originally supposed to be a solo comic done by David Herbert, updating every weekday (And sometimes on weekends) successfully. However, despite there only being thirty strips, David was repeatedly told by friends and pro editors that while they enjoyed his writing, his art was horrible. To make matters worse, his girlfriend dumped him around this time. His already frail ego shattered, Herbert quit the comic's art duties and hired Paul Salvi, which ended up making the comic much more successful than any of Herbert's other comics.
Sean Howard has claimed the reason A Modest Destiny has been on hiatus for over a year is he is no longer deep enough into Creator Breakdown to follow coherently from where he left off.
The author of Game Destroyers reached a point in the story where he grew to hate what he was writing, which led to two of the four hiatuses and a lot of Schedule Slip. This was eventually solved by getting past the horrible storyline and moving on to things which made more sense and allowed for more freedom.
Ever since Randall Munroe's fiance was diagnosed with breast cancer, xkcd has featured several strips dealing with cancer, ranging from Black Comedy to not comedy.
Teased but averted in-universe in Darths & Droids (a retelling of the Star Wars movies as a tabletop RPG). Jim and Annie (playing Padme and Anakin respectively - we know, we know, things just turned out that way) started Episode III with their relationship having gone sour, and with Annie really enjoying the roleplaying aspect it looked like a breakup would prompt her to make Anakin have a Face-Heel Turn and kill Jim's character in revenge. What acutally ultimately happened was that they reconciled; Padme still died but this was Jim actually roleplaying for once, using the death scene to give Annie more angsty material to work with.
John Kossler, author of The Word Weary, has no problem admitting that his entire comic is a way to cope with his depression humorously.
A little more backstory to this: A lot of Chris' breakdown was due to the fact that his Internet Trolls wanted to show him the reality of him wanting to officially produce his comic. Major cases of Schedule Slip, Chris fighting with a fan who didn't want him to use a character he made for shits and giggles, having a rival webcomic being more popular than his, all culminating when it interfered with his real life and angrily deriding his fans as those who'd just want more of his comics than him having a life. Which isn't much, but that's a different story altogether.
Lis Boriss of Broken Plot Device fame had her mother diagnosed with breast cancer. Lis's depression caused an unexpected indefinite hiatus, but luckily, surgery was succesfull, and webcomic came back very quickly.
Now her relationship of eight years has collapsed (though it appears to be ending amicably), and the strip is on hiatus again. The biggest problem seems to be how to deal with Sid, who is strongly based on her now ex-boyfriend.
He's also had issues with depression and anxiety in the past, which have on occasion caused him to take a day or two off from drawing the normal strip.
Nicholas Gurewitch of The Perry Bible Fellowship suffered a breakdown in 2008 when he put the comic on indefinite hiatus out of fear that becoming too dedicated to it would forever pigeonhole his career as only a webcomics artist. For some time, the final strip appearing on the site was "Catch Phrase", a rather dark and poignant comic (even by PBF standards) in which a TV personality commits suicide after becoming sick of the over-saturated popularity of his catchphrase, "Gee Golly Jeepers!" PBF would not return until over two years later, upon which Gurewitch began updating the comic again, albeit much less frequently than before. The "Catch Phrase" strip has since been removed from the official website but can be seen here.
Michael Poe, the writer/artist for "Errant Story," has been having a long run of bad luck for the last couple of years, culminating in his hospitalization in February 2013. Between his health problems and his wife's, it's hard not to wonder if there's some kind of ancient curse involved.
Hyperbole And A Half has suffered majorly from this, putting the comic on semi-permanent hiatus while the writer battles depression.