Euchre from TwoKinds just seemed to be forgotten about. After Trace's battle with a Neutal possessed Flora, he is never mentioned again, despite being a rather important and seemingly powerful character who was in league with the Master Spy. He might simply be Master Strategist in a magical disguise. In truth, he IS a Keidran that can disguise into a human down to the genes and with what seems to be some kind of double personality syndrome, since he helps Keidran while undisguised while leading the persecution in disguise. He has a half-human/keidran changeling daughter.
Sara was a barista at the Coffee of Doom who had a crush on Marten for the first few strips. She seemingly disappeared early on, when the focus shifted to Faye and Marten. This has been subject to a Lampshade Hanging on more than one occasion. The 'official' explanation for her disappearance is that she was eaten by an allosaurus, but really she was just a boring character.
The trope is often lampshaded and subverted in this comic. Members of the supporting cast regularly disappear — often for extended periods of time — without warning, and are later given explanations when another character wonders why they are gone. Most (with Sara being one of the only exceptions) will turn up again up to 500 pages later.
Even the infamous PizzaGirl reappears after a long absence.
In El Goonish Shive, some of the side characters have fallen into this. And of course, let's not forget Lord Tedd, hinted in the past to be the Big Bad of the entire strip, has not been seen in years real-time. Dan Shive said he introduced the character too soon, which is why it vanished. However, it looks like Lord Tedd may be coming back.
Early in Kevin & Kell, Lyndesfarne was friends with a turtle and an armadillo, the gag being that they were the only three herbivores who could hang out at the mall food court. Conina the armadillo is also at the school dance, and then we never see either of them again.
Now that Dresden Codak has gone from Kim being a teenage Mad Scientist living in a big house just outside a city on the Pacific coast to being a penniless mad scientist in her early twenties living in a small room in a Vast Bureaucracy, it looks like we won't be seeing anything more from Alina, Dimitri and Tiny Carl Jung for the forseeable future.
PvP does it so much it should be called Kurtzing. The entire cast from Samwise except for Skull, Francis' gaming troupe, Skull's gaming persona who later became his own character, Jade's former staff from when she created a feminist magazine, Jade's High School best friend, Robbie's former best friend Jase, Reggie who was Miranda's blind boyfriend, Miranda who was Reggie's hot girlfriend (redacted, though she was brought back by a guest strip so Kurtz wouldn't have brought her back if not for that strip so it doesn't count so HA), Miranda's big dumb boyfriend (whom she presumably left because he wasn't dumb any more), a talking arcade machine, Newt-boy, a funny talking rat, Francis's robot, Skull's cousin Sheckie, Sheckie's girlfriend, a divorced woman who was implied to be a recurring character, Cole's entire family (though a divorce was mentioned in passing), the game-store witch, and the giant Panda. That's more than 20 characters that fit this trope. Gwen almost fitted, too, until she became an expy in Kurtz' other strip, "The Trenches".
Penny Arcade, with its infamous "no continuity" policy, quickly phased out the few non-Gabe-and-Tycho characters it introduced shortly after they appeared, notably Chuck/Charles and Div.
Sonichu has this all over the place, as new characters were created to be analogues of people who tormented the creator in Real Life. Most characters just disappear, getting squeezed by the Kudzu Plot.
Shauna from Bad Machinery had an older brother; the only explanation of his disappearance is, in an answer from John Allison to a question on Tumblr, "Chuck Cunningham’d."
Ménage à 3 occasionally introduces plot elements that just don't come to anything. Some are simply one-shot characters, but others might have been expected to reappear.
In the early days, two such elements were Eulice the terrifying landlady and Rob the agoraphobic neighbor. Presumably the writers couldn't think of much more than one joke each for them. Eulice did reappear briefly in 2014, however.
Junghan the comics shop manager (best friend of lead character Gary and boss of other lead character Zii) also seemed to be a Syndrome sufferer, but made at least a brief return after a couple of years' absence from the comic, and even showed up for a brief but effective crossover appearance in spin-off Sticky Dilly Buns.
Takeru Oyama, famous manga artist and father of the fairly major character Yuki, made one appearance in a few strips in March 2012. He was subsequently reported to have been mentoring lead character Gary for a week after that, but then he dropped off the face of the comic. He presumably flew home to Japan, which would excuse his vanishing, but when last seen he apparently believed that Gary and Yuki were all but engaged.
Characters regularly come and go as Agatha the eponymous Girl Genius travels about Europa, but Klaus Wulfenbach's second in command Boris Dolokhov notably has vanished from his position without explanation following Agatha's in-universe two-year time-skip.
Awkward Zombierepeatedlylampshadedthis trope with Roy's mysterious disappearance from Super Smash Bros... Every time a new character was announced for Smash Bros. Wii U, the comic would lampshade just how much he was left behind. In this comic arc, made after Roy was confirmed for DLC, we realise that he's been gone so long that only Marth and Pit seem to remember him.
In Boy Meets Boy Harley's "best friend" Aubrey just suddenly disappeared entirely with no explanation once Harley's bandmates, Skids and Cyanide, pretty much took over her role. Much, much later in the comic, however, Aubrey suddenly reappears with her disappearance being accredited to going through gender reassignment therapy, after which male-Aubrey remains in the comic for its duration.
In Irregular Webcomic!, the Fantasy and Space themes (and, extremely early on, Cliffhangers) operated on the conceit that they are Tabletop RPG campaigns, complete with a GM. This was soon dropped from Cliffhangers after the GM made only two appearances there, but Fantasy and Space continued maintaining this. Gradually, the GM started appearing less and less, until his final appearances in the Space and Fantasy themes ended up being No. 1651 and No. 1662, respectively. The last time the GM was ever mentioned was in No. 1935, when Space's Paris character gets fed up with a Timey-Wimey Ball situation and starts calling for the GM, only to get no response. (Of course, this was months after the Author Avatar had killed himself...)
Not in My Backyard!: Terrance the armadillo largely disappeared after the first few months. After that, the secondary characters vanished one by one, leaving just Oscar, Oliver, Bip, and Bap.
Bound Adventures dropped Prince Balin after the first adventure, despite him being Princess Irina's lover and responsible for her rescue in that story.