Tiny Toon Adventures brought Bosko, Honey, Foxy, Foxy's girlfriend and Goopy Geer back for cameos, in which they were hailed as talented veteran cartoon stars. Later, an episode of Animaniacs had Buddy make an appearance, but it was a lot less complimentary toward the character in question (turns out Yakko, Wakko and Dot were created just to spice up his notoriously boring cartoons).
Bosko, the original Looney Tunes star, very rarely makes appearances in modern Looney Tunes artwork, and hasn't appeared in any cartoons since his redesigned cameo in Tiny Toons. Understandably, this is due to his roots as a blackface character making him an unacceptable character to put into the mainstream today. It dosen't help that his esoteric nature compared to the mainstream Looney Tunes (due to his cartoons being off the air since the 1980s), not to mention his vague personality, do not make him a popular character among fans.
Bimbo the Dog from the Betty Boop cartoons. In the early shorts he was meant to be Betty's boyfriend, but come 1934, and the Hays Office objected to an interspecies relationship, forcing Fleischer Studios to abruptly drop Bimbo. He would never be seen again in the series.
Star quarterback Brick Flagg from Kim Possible showed up here and there, but he sort of vanished after a while. Although his no longer appearing was eventually justified at least for the last season, he graduated by then. He wasn't exactly the brightest bulb when off the football field, and it was mentioned that he'd finally graduated after being held back a few years. (He even votes for one of his opponents during the school election. Not that it mattered much.)
After the rights to Thomas the Tank Engine were acquired by HIT Entertainment, and some of the original producers left the show, several semi-regular characters, such as Duck, Oliver, Boco and Daisy, were dropped. This also happened to several one-off and recurring original characters due to a need of merchandising. Season 17 and onwards however, seems to be slowly reinstating them back into the series. This trope can now be said to apply to the Logging Locos, whose main entrance way into Sodor was seen boarded up in several episodes without any explanation.
Even outside of the many incidental cutaway characters, Family Guy has a few.
The trope is directly lampshaded in the episode "The Father, the Son and the Holy Fonz", in which Peter starts a religion based on Happy Days.
Peter (preaching): Let us contemplate the mystery of Richie’s older brother Chuck, who ascended the stairs with his basketball in season one, and never came down again.
Brian's gay cousin Jasper, who used to appear a couple of times per season, disappeared after the gay marriage episode.
Jasper appeared in the episode "Brian's Play" talking with Brian on Skype and the episode "Life of Brian" at Brian's funeral.
Joe Swanson's own children seem to disappear without a trace. Kevin Swanson appeared in the first 3 seasons, then just disappeared for years, though he had a few non speaking cameos. Years later after his last speaking role Peter questioned about his disappearance out of curiosity. Joe explained Kevin died as a soldier in Iraq with hardly any emotion. Seth MacFarlane felt Kevin was not a very interesting character to write for. Kevin is brought back as MIA in a new episode.
Parodied in Spies Reminiscent of Us when Chris enters in an exchange program to be replaced for an Elephant (don't ask). at the end of the episode Brian stated that it was a joke for the episode.
In Carol Pewetershmidt's first appearance she had just given birth to a baby boy, in her recent appearance he is nowhere to be seen.
Chris was set up to be with a girl named Anna in "Long John Peter" but, after that episode, she's never mentioned again and Chris is seen trying to get with other girls after that. That also happened with Herbert's niece in the Valentine's Day episode.
Knowing who voiced Anna (Amanda Bynes) there is no way she will return to the series!
Nurse Gollum from Season Two (other than a voiceless cameo in "Freak Strike"). However, there's a good explanation for why she was removed from the show.
Dr. Mephesto and Kevin. They were main characters in the first 3 seasons, but disappeared early on in the fourth. One of them DID, in fact make, a one-off apperance in 201 but has not been seen since. Parker and Stone have stated, however, that they grew tired of Mephesto and had wished they'd written him off completely in season 4.
Some of the children's parents that aren't Stan, Kyle, Kenny, Cartman, Butters, Token, Wendy, etc, have been replaced with different people.
Midget Wearing Bikini and other joke news reporters seen in the earlier seasons were phased out in favor of just using "Tom" or parodies of actual reporters.
Mephesto's son Terrance was introduced as The Rival to the four boys, along with his sidekicks Bill and Fosse. Terrance quickly faded into the background, as did the other two. The three are still occasionally seen as background characters, but lack their signature thick eyebrows. Craig, Clyde, and assorted other boys now play the part of the rivals to the main four.
Mr. Wyland, the substitute teacher.
Officer Barbrady: Effectively replaced by a full police force around season 7, though he is still brought back for small appearances every now and again.
Lampshade Hanging in "Cartman's Incredible Gift" when Ms. Crabtree is murdered by a serial killer.
Lou: "I owe it to that victim over there! I know she hadn't been in any recent episodes, but DAMMIT, she deserved better than this!"
Damien hasn't reappeared in years (aside from background cameos in the gymnasium at times, or being seen on a TV in "Tsst!") despite his father making numerous reappearances.
Nurse Goodly (the nurse with no arms from "Cartman's Mom Is Still a Dirty Slut") hasn't made a reappearance in scenes taking place in Hell's Pass Hospital.
Lampshaded in the second season of Freakazoid!. Lord Bravery and the Huntsman are upset about their sequences being trimmed down to nothing in the second season and want something to do. Freakazoid makes them wash his car and that's the last we ever see of them.
Ironically, Freakazoid's alter ego, Dexter Douglas is only seen twice in the second season and never shows up again.
Remy Buxaplenty, rich bastard and Juandissimo's godchild on The Fairly Oddparents, is an odd example of this in that he is written out of the show at the end of his first appearance. Three seasons later, apparently due to viewer demand (and because he was one of the creator's personal favorite characters), he returns as a recurring antagonist to Timmy for three more episodes. After the third one, though, he's not mentioned again, not even in Juandissimo's subsequent appearances.
Also, back when Mark Chang was Timmy's enemy he had two friends on Yugopotamia named Jeff and Eric. They haven't appeared recently, not even in an episode that had Mark going back to his planet temporarily.
On Space Ghost Coast to Coast, much of the Council of Doom disappeared without a trace. The most obvious examples are Metallus and Black Widow. Lokar disappeared after "Waiting for Edward", and after "King Dead", Tansut was never seen again.
The Creature King suffered this the worst. He was closest thing the sixties series had to a Big Bad. He was the main head of the Council of Doom and fought Space Ghost more times than any other villain. Yet he never appears in Coast to Coast, unless you count stock footage from "Jacksonville".
The Simpsons: After The Movie and a brief appearance in the opening of the 19th season premiere, Colin was never seen again and Lisa is back to being single. Yeardley Smith actually voiced her annoyance at this, arguing that Lisa deserves "to keep this one."
Lionel Hutz and Troy McClure were both retired after their voice actor Phil Hartman's untimely death. Since 1998, they've disappeared from Simpsons canon (with the very occasional exception of a crowd scene). Hutz's role as the Simpsons' incompetent family lawyer was taken by 'Old' Gil Gunderson.
Early episodes had two - almost identical - characters called the Weasels do Nelson Muntz's bidding. Sometime around the third season, they disappeared and Nelson became friends with the Jimbo, Dolph and Kearney trio. The producers explained on the DVDs that six bullies felt like too many.
They make their first appearance in years in "The Winter of His Content" where it's revealed they moved to Shelbyville.
Homer's half-brother Herb seems to be this as well. He made appearances in two early episodes, then never appeared again. The series occasionally will quip about this, such as once when Homer makes a passing reference to "my seldom-seen half brother Herb."
Herb makes a speaking cameo on Homer's answering machine in Season 24's "Changing of the Guardian" in which he reveals that he is poor again.
The secondary Channel 6 newscaster Scott Christian was quietly phased out after Kent Brockman became recognised as the much funnier character. Ironically, a running gag was suggested that Christian would always be covering for a perpetually absent Brockman, despite the Action News show being named after the latter. One instance of this was trialled in season 1's "Krusty Gets Busted", but was soon rejected, and Brockman does actually appear later in the same episode.
Serak was in the first Treehouse Of Horror along with Kang and Kodos, who appeared in all subsequent Treehouse Of Horror episodes, but Serak didn't. Perhaps this was as James Earl Jones could not be gotten back to voice him.
One episode have the Simpson family adopt another dog, She's the Fastest, as Santa's Little Helper fell in love with her, and they have puppies together. She mysteriously vanishes and is never mentioned again.
Herman, first seen in Bart The General, was supposed to be a recurring character, his gimmick being that each time he showed up he'd give a different story of how he lost his arm. Aside from a few cameos, he's never been seen again, and how he lost his arm was resolved in a flashback episode.
Several recurring characters in King of the Hill just disappeared over time like Eustace and his geeky son Randy, who were rivals to Hank, Bobby and their friends in the earlier episodes but they vanished over time too. Bill's iguana Lenore only makes a one-episode appearance, and his girlfriend Laoma, who was Kahn's mother. A season finale episode ends with her living with Kahn and her and Bill in a relationship, but come the new season she's inexplicably gone. The writers apparently wanted to keep Bill alone and miserable.
In the episode in which Bobby breaks up with Connie, he meets a new girl named Debbie at the mall. They get along fine and are set up to be a couple; come next season she is never seen nor mentioned again and Bobby is back to being single. This happened quite a few times, actually: Bobby would meet a new girl who clearly liked him and they are seen together at the end of an episode. Invariably the girl is never seen or mentioned again.
Theres also the blonde kid Garth, who appears in the Straight Arrow episode and is implied to be Boomhauer's illegitimate son.
In the second episode, "Square Peg", Peggy is seen talking to several other women on a bench at a Little League game. Come the next episode, they have vanished and Peggy's only friend is Nancy. This may have been a retcon for later episodes that had Peggy worried that she didn't have enough female friends.
Those women do appear in the episode in which Khan and his family move in three episodes later but as mentioned previously they don't appear again after that.
Those women appear again rather infrequently and at times not all together, one episode in season 2, Peggy's Turtle Song features them delivering a very bizarre Laughing Mad moment.
In some of the earlier episodes of SpongeBob SquarePants, Spongebob had a pet scallop in a bird cage above his bed. He was never seen interacting with it, though, and during the middle of the second season it vanished. This was referred to in one of the video games when in Spongebob's room when you click on the cage, he says something along the lines of "That's where I kept my pet scallop, I think he ran away".
Which is weird, in that it has been seen in later seasons, too.
Also Bubble Bass, who appeared in a couple episodes back in season 1 but has never been seen or mentioned since.
Apparently Bubble Bass was placed on a very long bus ride, because he had an appearance in the Season 8 episode Plankton's Good Eye.
And not to mention, Flatts the Flounder, who was the bully at Mrs. Puff's Boating School. He only appeared in three episodes, (one of them where he made a major role) and never appeared after that.
Several characters in The Animals of Farthing Wood who weren't killed off, but simply disappeared in Season 3. this includes Fox and Vixen's son Friendly, Kestrel, and the surviving blue foxes aside from Ranger.
Friendly made a brief appearance in the second episode of Season 3, then was absent for the rest of the series without explanation. Word has it that the show's producers didn't like him and requested that he be dropped from the show. Kestrel's disappearance is actually consistent with the original novels, in which the character simply stops appearing around the fifth book in the series, with no specific departure arc.
In the original run (1991-94) of Rugrats, two slacker teenagers named Larry and Steve were seen from time to time with a different job in every appearance. After the show's hiatus, they disappeared; in a much later episode, Larry appeared as a doughnut salesman and is never seen again.
Timmy McNulty and his siblings also disappear from the series, sometime around the prelude to Rugrats in Paris and the introduction of Kimi Finster.
In the Jumanji cartoon, the villainous "Stalker" character was introduced in the sixth episode, who looked somewhat like the Grim Reaper. The other villains feared and worked for him, which seemed to be setting him up as the main villain of the series. Unfortunately, he only appeared in two episodes and never reappeared, despite the ending of both episodes hinting at a reappearance.
In Walter Lantz's The Beary Family, the family originally consisted of Charlie (father), Bessie (mother), Junior (son), Suzy (daughter), and their pet goose, Goose. Early into the series, Goose disappeared, then eventually Suzy was dropped without explanation.
In The Blue Racer, the main character chased after a racially insensitive Japanese Beetle (yes, a racist Japanese caricature depicted as a beetle). The Beetle character was dropped halfway through the series. Gee, I wonder why...
Franklin is rather bad for this, but perhaps the worst example is the character of Moose. An entire story in the first season of the program, based on of the books, was dedicated to introducing this character and his acceptance within the close-knit community. In the episode, he finally joined Franklin's class and became his good buddy, but he was never again seen on the series and no explanation whatsoever was provided for his absence.
Officers Julia and Cliffany from Bob's Burgers suddenly disappeared after Season 1, but they did make a few non-speaking background appearances in some episodes.
Popeye had four nephews introduced around 1940 - as the series went on it was knocked down to three, then two. This was probably due to animation cost restraints, but it comes off as pretty creepy.
Hanna-Barbera's take on Popeye in 1978 brings back three of the nephews. But in 1987's ''Popeye & Son," the nephews and even Swee' Pea are egregiously left out in favor of Popeye and Olive having a son.
Dora the Explorer showed that Diego had an older sister named Daisy. She was replaced with Alicia once he got his show, even though the episode she was in revolved around her birthday.
Lampshaded in an episode of Animaniacs, where Rita and Runt are advertised as "Missing" on a milk carton (the "Rita and Runt" segments having been dropped in the latter half of the series' run, after which the characters themselves put in the occasional cameo appearance, but gradually disappeared - though they continued to feature in the opening credits, and were eventually restored for the direct-to-video movie "Wakko's Wish").
Minerva Mink's disappearance was more justified. Her cartoons were too risque, even by Animaniacs standards — of the two that actually aired, one had a nerdy werewolf who turned into a hunk under the full moon; the other had Minerva using her sex appeal to dispatch a dachshund named Newt — and the executives were afraid she'd be used in a lot of sexually unsavory fan art and fanfiction online. This ended up being a fool's errand, as this became Minerva Mink's fate anyway, thanks to those two episodes. It would have been easier to not have made Minerva a character in the first place.
In the final season of Teen Titans the Brotherhood of Evil recruits nearly every villain that ever appeared in the series. While the appearance of some in the initial lineup is a Snapback from the last time they fought the Titans, some such as the Nufu Source didn't appear in the final battle while Kitten wasn't seen after her encounter with Starfire.
Both of which can be easily explained - Kitten was just a spoiled brat, and Cyborg ATE the Nufu Source. However, some of the villains that the Brain called were actually killed somehow.
Speaking of the Brotherhood of Evil; the Doom Patrol, who were the Brotherhood of Evil's original enemies in the first place, are basically written out after "Homecoming Part 2". What happened after the Titans intervened? The Brotherhood of Evil basically focused on getting rid of the Titans. The Doom Patrol weren't even there to help, nor they were mentioned.
In the first episode, arch-villain Slade is always seen with a silent butler standing at attendance - possibly Wintergreen, Slade's butler in the original Teen Titans comics. He was not used again after this episode.
The H.I.V.E. Academy Headmistress was a bizarre example, as her first (and until the series finale, ONLY) appearance, she seemed to be set up as a Big Bad in charge of training teen supervillains. When the H.I.V.E. organization resurfaced in later seasons, she had been usurped by Brother Blood with no real mention of what happened to her. She returned in the series finale as part of the big final showdown but was quickly dispatched. She later appeared in the comic alongside a new trio of teen villains, but was quickly Bound and Gagged by Robin and presumably arrested. In all of this, it was never explained exactly what had happened that lead to her being booted from her position at the academy.
In The Critic webisodes, ALL the characters from the TV series have disappeared (save Jay Sherman and a brief appearance by Vlada). The worst of all this is that Jay's girlfriend Alice Tompkins is replaced with a Replacement Scrappy named Jennifer.
The Legend of Zelda was based chiefly on the original game in the series, with bits of Zelda II: The Adventure of Link. Despite being a prominent part of the backstory for both games (indeed, she was the reason Link took up his famous quest in the first place), Zelda's nursemaid Impa is not included in the cast. She did, however, feature prominently in the comic book series which launched at approximately the same time.
Also, the Triforce of Courage is never mentioned in the animated series either (the Triforces of Power and Wisdom can count as characters; they even have voices!). As with Impa, Courage is mentioned in the comics and other books (though never seen; it is said to be "in Link's heart") that were otherwise similar to the cartoon.
In American Dragon Jake Long, Rose was separated at birth from both her parents and her twin sister to be raised by the Huntsclan. After the Huntsclan is erased from existence (long story) we catch up with Rose who in the revised timeline lives a normal life with her parents...and no twin sister. Apparently the sister's whereabouts would have been a plot point had the series been given another season.
In the original Teenage Mutant Ninja Turtles cartoon there was an episode involving a female lizard mutant named Mona Lisa. She serves as a potential girlfriend for Raphael and helps him fight off hijackers who were responsible for her mutation (she was originally a human); at the end they say their goodbyes and she secretly follows Raphael and April to the turtle's lair and introduces herself to the rest of them. Despite this being a setup for her being a recurring character and being a fan favorite she is never seen or mentioned again.
That cartoon used to pull the same schtick all the time. They'd have an episode that seemed to set up a new cool character, then they'd usually disappear forever. Remember Metalhead? And Muckman and Joe Eyeball?
Several notable recurring characters, some of which had been on the show from the beginning, just disappeared during the show's 7th and 8th seasons. Season 7 saw the final appearances of the friendly teenage aliens the Neutrinos and the Turtles' young friend Zach. In season 8, Irma, Vernon, Mr. Thompson, and Casey Jones made their last appearances and then vanished without explanation. Bebop and Rocksteady disappeared after season 8, even failing to appear when Shredder and Krang returned for a story arc in the final season with no explanation for the bumbling duo's absence.
On Hurray for Huckle / Busy Town Mysteries, the Hilda Hippo character appears in the opening credits and appears in one or two stories as part of the mystery-solving team, but is absent from all other episodes.
In a couple of episodes of Arthur, George has a slightly younger sister; she last appeared in the Christmas special and so far has not appeared again.
There's also D.W.'s pet toad "Toady Wartface"; after its introduction it made only one other appearance.
Semi-justified because her actress, Billie Lou Watt, died around that time.
The second episode of Nickelodeon's Doug, "Doug Can't Dance", had Roger leading a different group of thugs than usual. These thugs appeared only in that episode.
X-Men: Evolution: After the rise of Apocalypse, Sabretooth just disappears from the show. While its given a small Hand Wave courtosy of Pyro (claiming he was 'playing with a ball of yarn somewhere'), it's more of just Pyro rambling and doesn't mean a thing. Similarly, Destiny disapears in season 3 without any mention. When she last appeared she tells Mystique that she'll be involved in a plot to bring back an ancient mutant, but by Mystique's next appearence, she's working with Mesmero to bring back Apocalypse without any mention or reason.
In the TV series for Barnyard, titled Back at the Barnyard, Otis' wife, Daisy, and their son Ben Jr. are completely absent from the show, Daisy's been replaced by a new female cow named Abby; the strange part is Daisy's best friend Bessie continues to appear on the show.
Why does everyone always forget the donkey from the movie?
Stereo was written out of the second season of Space Goofs.
In Blazing Dragons, Sir Galahot and Sir Hotbreath, two of the Knights of the Square Table, never appeared in Season 2, in which the main focus was on Flicker, Loungelot, Blaze, and Burnevere, but Allfire, Griddle, Flame, and Count Geoffrey and his minions all had some appearances.
DuckTales notably had quite a few recurring characters disappear without any explanation during its second season, including Doofus, three of the Beagle Boys (Bankjob, Babyface, and Bugle), and Donald Duck and Admiral Grimmitz.
Happens frequently in Transformers G1; over time several characters from the 1st and 2nd season stop appearing after the movie and later seasons in order to focus more on the new characters. Having Loads and Loads of Characters and the show being Merchandise-Driven its easy to forget and lose tract on who's who. This meant characters who actually survived, such as Huffer and Sunstreaker, disappeared into thin air and reappeared in the realm of fanfiction forever. If your toy wasn't on the shelves at the time you were liable to simply cease to exist without a word. The third season was even more confusing to Japanese viewers, because Transformers: The Movie wasn't shown in Japan until later.
Ewoks in the case of Paploo. In the second season, he was reduced to a background character and the leading four does not even seem to notice his absence from their adventures.
Hey Arnold! had a few. Anybody remember Ruth P. McDougal (the sixth-grade girl Arnold had a crush on, though she could have graduated. She wasn't seen much after the Valentine's Day episode where Arnold tries to go on two dates at once and finds that Ruth isn't the dream girl he thought she was, as she was very boring, very shallow, and not very bright) or Mr. Smith?
The first episode with Coach Wittenberg mostly revolved around his son, Tucker, and Arnold helping him get his father's approval. Tucker vanished after that, even though Coach Wittenberg continued to appear, along with the introduction of his (ex-)wife Trish (presumably Tucker's mother?) Tucker didn't even show up when the two remarried.
Harvey the mailman is pretty much one. He appeared regularly from 1996 to 1999, but by the Turn of the Millennium, he hardly ever appeared on the show, making only background appearances here and there. For unknown reasons, Harvey's voice actor Lou Rawls stopped doing voice work for the show after the Season 4 episode "Chocolate Turtles."
After the Dexter's Laboratory episode "Trick or Treehouse", Mimi and Lee Lee were no longer seen or mentioned (although they were generally carbon non-white copies of Dee-Dee anyway).
Mandark's sister Lalavava, was never seen or mentioned after her appearance.
Come to think of it, after Season 2, whatever came of the Justice Friends Val Halen and The Infraggable Krunk?
They show up in season 4's "Dexter's Wacky Races."
Action Hank and The Pony Puffs (Dexter and Dee Dee's heroes, respectivly) also seemed to have taken their leave after Season 2.
Then there's Douglas P. Mordechai III, Dexter's friend from the schoolbus. He only appeared in three episodes. Justified in that few episodes from Dexter's Lab took place at school.
My Little Pony And Friends had an ever-changing cast, as they tried to market as many ponies as possible. There were some characters that never faded like Wind Whistler or Fizzy but others disappeared without a trace. Notoriously none of the ponies from the first special ever pop up again. You'd think they'd have a close bond to Megan or would at least pop up more, considering they saved the entire kingdom. Whenever the ponies go snatch Megan, she never says "Where's Firefly? Or anybody who was here last time?"
It's most notable with the "baby" versions of several ponies. It's not 'til the TV series gets underway that they're treated like the toyline treats them (as daughters of the adult ponies they're named and designed for, existing alongside them.) This introduces a serious hole to the second special: it has has baby versions of two characters from the first special and two who will appear in future installments. If those are their daughters, then how come they're never, ever seen alongside their mothers? (Of course, maybe the ones whose adult versions were yet to appear are the same characters grown up; at least, that's how the fandom treats it.)
I.M. Weasel's sexy nurse, Loulabelle, made her debut in the season 2 premiere, but was not seen or mentioned since the season 3 premiere. It was already implied in one episode that she didn't like Weasel, so that's one reason . The more likely reason was Cartoon Network didn't approve of the dumb blonde stereotype she perpetuated.
Odd since one of the main characters in Ed, Edd n Eddy was one (Nazz), though she doesn't show up as frequently as the other characters.
KaBlam! had a number of these. Sniz and Fondue's room mates, Bill the Lab Guy's daughter Quirky from Action League and Grubby Groo from The Off-Beats (The only adult in that entire short!).
In Rocket Power, the Rocket's neighbors, the Stimpletons, appear a lot less in Season 3, almost to the point of cameos, actually. Also, how often do you see Mackenzie during that season, either?
In Chip 'n Dale Rescue Rangers there was one episode where Dale falls in love with a bat named Foxglove, who loves him back. Chip is also happy because he gets Gadget all to himself. Foxglove was never seen again, though she seems to appear in more Fan Fiction than not.
Disney Afternoon shows regularly only had a small number of recurring characters while most other characters, even main characters are limited to one episode. These one-shot characters, however, sometimes gained a lot of popularity and fans of their own, sometimes more than some main characters. Chip 'n Dale Rescue Rangers had some more popular one-shots including the squirrel Tammy, the lab rat Sparky, Gadget's Evil Doppelganger Lahwhinie and Gadget's father Geegaw who is only ever seen in a picture. This popularity mostly rose long after the show was produced in a time when there was neither a vocal fandom nor an appropriate means of communicating the popularity of a character to the makers, so none of them ever returned. Both Foxglove and Geegaw eventually returned in the Boom! comics.
In the second season of Jungle Junction, Carla the koala vanished completely.
Alejandro did appear in the first episode of Revenge of the Island still trapped inside the Drama Machine after what happened to him in the finale of World Tour and is confirmed to return to compete in All-Stars, while Blaineley was likely absent due to her almost unanimous hatred in the fandom.
Laura Limpin aka the Big Badolescent from Codename: Kids Next Door made 2 appearances in season 1 and vanished until a cameo in the finale (5 seasons later).
My Little Pony: Friendship Is Magic: Twist, Applebloom's best friend in "Call of the Cutie". They have a bit of fallout when Twist gains her cutiemark while Applebloom doesn't (Twist even says "We can still be friends, right?"), and for the rest of the show Applebloom is spending all her time with her new friends, Sweetie Belle and Scootaloo. It really does come across as though Applebloom ditched her closest friend over what essentially amounts to pony puberty.
There's also Derpy. Originally a template meant to be pasted randomly in the background, her eyes were crossed in one episode due to an animation error. She became a fan favorite because of this, so the show's staff started making her a scripted background character in season 2. Halfway through the second season, she actually got a spoken scene and another character even addressed her by name. However, due to her name, her crossed eyes, her low voice (her voice actor thought she was a boy), and her klutzy nature, a group of Moral Guardians decided to interpret this as an attack against mentally disabled people. Because of this, her appearances got less and less common after her episode and she was almost phased out of the show entirely by season 3. However, she has notable appearances during the coronation scene in the season 3 finale, as well as being in the credits for Equestria Girls. As of Rainbow Falls she averted the hell out of this in full frame, cuing earth shattering Brony squees everywhere.
Averted with Princess Luna. After her release from her Superpowered Evil Side (hinted at Demonic Possession) Nightmare Moon, in the second episode, Celestia says they will rule Equestria together. However, Luna does not appear or is even referenced in any later episodes of Season 1. In Season 2, however, she is mentioned in the two-part premier, and only two episodes later returns in an episode that revolves around her, and has appearances in the finale, and even more appearances in Season 3, so for Season 1 we can say she was Put on a Bus instead.
The DiC seasons of G.I. Joe quietly wrote out the Crimson Twins (Tomax and Xamot), with no word what happened to them after the movie, other than that their business was shut down.
Though most of the characters from the movie made at the very least a cameo in the series once (even Scar did at one point), Nala, the other lionesses, and young Simba (surprisingly) weren't in a single episode of Timon & Pumbaa, though they did return in the sequels.
In SWAT Kats, we have a couple of examples. In all cases, the characters are likely still there, somewhere in Megakat City, but just never focused on.
Feral's second in command Steel. He is last seen being chewed by Feral in Enter the Madkat, and never reappears in the second season. It's been argued that Feral's niece, Felina, replaced Steel as her uncle's second in command, however they have different ranks and uniforms - Felina is only a lieutenant and Steel was a lieutenant commander.
Burke and Murray. Last seen briefly in Metal Urgency, they are never seen or mentioned again. The main reason for this seems to be the lack of any scenes focusing on Chance and Jake's civilian lives in the second season, and since Burke and Murray were created to antagonize the two in those scenes, when they went, so did Burke and Murray. The two were slated to appear in an episode that never got made, though.
Al the Kat's Eye News helicopter pilot. He's last glimpsed in a non-speaking role flying the copter in season one's Chaos in Crystal, and although the helicopter itself appears multiple times in many other episodes, Al himself is never seen again. However, considering someone has to be flying the aircraft, he is probably still there.
Dr. Street is last seen getting knocked out of a window in The Ci-Kat-A. He presumably could've saved himself by using his wings to fly to safety, and, indeed, this was what the writers had in mind, as they wanted him to return in another episode and team up with Dr. Viper, but the series was cancelled before the episode was finished.
Dr. Viper himself. After turning himself into a giant monster in Mutation City, he gets doused with anti-mutagens and disappears from both the episode and the series. His final appearance is in The Origin of Dr. Viper, but that's told entirely in flashback. As mentioned above, though, he was scheduled to reappear in an episode alongside Dr. Street, but then the show was cancelled.
Bizarrely, the SWAT Kats' own arch-enemy Dark Kat. He gets away at the end of Razor's Edge in season two, vowing to return, but apart from an alternate universe version of him in The Dark Side of the SWAT Kats and a cameo as a cardboard cutout in The Origin of Dr. Viper, he never reappears, nor do any of the known unfinished episodes involve him.
In an example of Early-Installment Weirdness, there are a lot of reporters besides Ann Gora seen in The Giant Bacteria, including two male reporters from Kat's Eye News and two from a different news channel called Inside Megakat City. Both male Kat's Eye News reporters get to interview Feral in two different scenes, but after this episode, neither they nor the other reporters appear again. Inside Megakat City vanishes and Kat's Eye News is apparently the only news channel of any importance in town, and, aside from one brief appearance by Tab Mouser (who vaguely resembles one of the reporters from The Giant Bacteria) in Unlikely Alloys, Ann Gora appears to be its only reporter!
This may be the fate of Vehicle Voltron in all Voltron shows post the original 1984 series. They don't get so much as a shoutout in either The Third Dimension or Voltron Force. Possibly it's a reflection of the lack of popularity of the Dairugger XV derived segment and World Events Productions reluctance to spend money retaining the rights to it.
Ever since "Red Throne", Flame Princess hasn't had another major episode appearance in Adventure Time, despite being mentioned in "Breezy" and having a cameo appearance with Cinnamon Bun in the upcoming "Princess Day".