Pretty much any webcomic that has Cerebus Syndrome will elicit this reaction from old fans.
Many claimed that Ctrl+Alt+Del Jumped The Shark after Lilah's Miscarriage, pretty much since the day it happened. Then again, since half the people complaining never liked the strip in the first place, it's hard to tell if that was really the strip's actual fans that felt that way, and the notoriety of the storyline seems to have just given them something specific to vent their rage on.
As a minor note, the strips in question were complained about for having possible Cerebus Syndrome material mixed in, which is not a good junction to be at.
For a while, the Gunnerkrigg Court fandom had a distressing tendency to project that the future of the comic would be exactly the same as the latest page or two, and then use this as the basis to declare that they didn't like the new direction the comic was taking. In every case, said "new direction" was more like a brief detour. For example:
Some fans complained about post-Chapter-14 Annie Character Development ... upon seeing the very first page of Ch 15.
Some fans complained that the brief "Metal Gear Theater" interlude was a sign that the comic was descending into a mess of Dadaist nonsense and pop-culture references.
Note that any such comments should be taken with a grain of salt since most of the comments tend to be a bit on the snarky side.
Quite a few people vowed to stop reading Gunnerkrigg Court when Kat was confirmed gay/bi and went to great lengths to affirm that they didn't see it coming.
While there is a fair amount of disagreement about exactly when or why Dominic DeeganJumped The Shark, be it the Super Greg arc, the vacation arc, or the March on Maltak arc, a consensus seems to be that the comic was Ruined Forever by Mookie's characterization of Siegfried after his death and transformation into a demon lord's servant and has only gone downhill since then.
Erfworld is promptly Ruined FOREVER whenever anything that seemingly violates the rules of the setting occurs on the grounds that it's a Deus Ex Machina, or whenever the tide seems to turn unexpectedly against the "good guys".
Ruthlessly parodied in Shortpacked!. Poor Ethan is constantly being confronted by obsessive toy fans crying "It's ruined forever!" over the most trivial things.
One of the most notable examples is the reaction to the "Hivebent" arc, which shifted focus away from the main characters at a point of high dramatic tension to develop a large group of internet trolls, who had for the most part had either secondary roles or not appeared at all. Part of the complaint stems from the fact that opposed to the fairly subdued main characters, the trolls spend much of their time killing each other, making out, or crying about either of the above. It caused a massive fanbase shift, and early adopters had to deal with suddenly being outnumbered 4:1 by a crowd that thought this was a comic about trolls and their funny human friends.
Some people have been feeling this for UU/uu after the reveal, especially with the initial shock. The new trolls aren't trolls, but they're called Cherubs? They look like Lord English, really ugly! RUINED FOREVER
Some fans of the wackier, less serious Problem Sleuth didn't take kindly to Homestuck's more plot-driven storylines.
Sometime when Zoophobiastopped updating regularly, it suddenly became ruined forever in the eyes of some fans and critics, not unlike what would later happen with Steven Universe. All of a sudden, the once-praised art, characters, and story started getting criticized to hell and back. It got to the point where even the author was starting to agree, and she scrapped the comic to pursue other projects. She does have plans to reboot it in the future, so time will tell if it will become "ruined forever" again when that happens.