In a sense this has happened twice with Aqua Teen Hunger Force. In the Space Ghost Coast to Coast episode they originated in, they were a team of mascots for a corporate food chain that Space Ghost sold out to so he could buy a boat. When the spin-off series was made, the characters were heavily changed, the corporate mascot part was dropped, and they were made a detective agency just to have a premise to give to executives rather than calling it a show about food people just... doing stuff. That at least made them a force, but when the detective work was inevitably dropped from the plot, they weren't even that.
This was always fully acknowledged; [adult swim] included bumps stating the following;
First off, they aren't teens. And there is no water involved. And that whole "Hunger Force" thing? That's probably misleading, too.
With the yearly re-titling of the show, this does not apply as much. The current season of the series is titled Aqua TV Show Show, for example.
Although technically, the trio are still heavily involved with water: Carl's pool.
Looney Tunes. When the series was first conceived in the early '30s, it was meant as a showcase for songs in the Warner Bros. music library (and as a competitor with Disney's Silly Symphonies series). By the mid thirties that concept was done away with and the "looney" part of the title began to take precedence.
Its sister series Merrie Melodies is doubly so, as for most of its run it has essentially been the same as the Looney Tunes. At first it separated itself by being one-off cartoons, whereas the Tunes used recurring characters. Then the Merrie Melodies went color, shortly after which they phased out the musical format. By the time Looney Tunes converted to color, the only difference between the two series was the opening theme music. This wiki doesn't even give them separate pages.
In the Tunes' case, it helps them the fact that "tunes" and "toons" are homophones in some dialects, leading some to believe the name is just an artistic misspelling.
To this end, there are some people who insist on referring to the series as a whole as "classic Warner Bros. shorts" or something similar.
To further confuse things, there has been merchandise where "Looney Tunes" characters such as Bugs Bunny and Taz are branded with "Merrie Melodies".
The Disney Princess franchise now includes Mulan, who is neither a princess by birth nor marriage. And to add further irony, not all the princesses are included in the line-up (Princess Eilonwy, anyone?)
For the longest time the episodes themselves being Halloween specials were archaic since they aired in November (thanks to Fox's contract with MLB pushing back the release dates), something the show itself even joked about several times. This seems to have become more lenient however, as more recent "Treehouse" episodes have begun airing in October again, thus undoing this trope.
Averted with The Venture Bros., which ended the first season on a cliffhanger. Fans were left wondering how the show could continue to exist with its title characters killed off, until the question was resolved the next season.
The opening episode of season two even had a Red Herring to the effect that the show would be about Rusty and his newfound brother Jonas Jr., technically still the Venture Brothers of sorts. Then, Hank and Dean got better.
To a degree this still applies, since the central character is now the boys' father Rusty, not the boys themselves (though they are still prominent).
Ben 10. Originally so dubbed because protagonist Ben could turn into 10 different aliens. It wasn't long, however, before he discovered an eleventh, and by the time the Sequel Series rolled around, the concept of only ten alien forms was gone. Nor was he 10 years old any more in the sequel.
While the title My Little Pony always made sense for the toys, it makes less sense for the various animated series, as the ponies are neither little nor owned by anyone. My Little Pony: Friendship Is Magic, at least, has tried to Title Drop the name by having ponies use the phrase among themselves.
There is a strange example in Friendship is Magic of an artifact character name. Discord was first introduced as the Arc Villain of the season 2 premiere, and as his name would suggest he got his kicks out of causing, well, discord amongst ponies. The trickster god promptly became a fan favorite and his voice actor John de Lancie expressed an interest in voicing him again, which led to Discord returning and being reformed in season 3, without losing his now unfitting name. At least, until we get to know the "good" Discord better. He is a shining example of Reformed But Not Tamed.
G4's Fluttershy derives her name from a G3 pony who was named for being a "shutterfly", ie a photography enthusiast, which the G4 version is not.
By the second season of The Replacements, the show focused mainly on the wacky misadventures of the Daring family and less on Todd and Riley replacing people in their lives.
Gargoyles had an in-universe example with the recurring antagonist "Coyote". He only had the name because, in his first appearance, he was a human-looking android disguised as David Xanatos and styling himself as the sixth member of The Pack, an animal-themed group that already included a "Fox", "Wolf", "Hyena", "Jackal" and "Dingo" in its lineup. He eventually ditched the human disguise and abandoned The Pack to serve as Xanatos' henchman full-time, but he never stopped calling himself "Coyote".
Word of God indicates that he was also slated to be a major antagonist in the planned spin-off Gargoyles 2199, which would have taken place long after The Pack's death.
When The Land Before Time reached Brazilian audiences, it was under the title "Em Busca do Vale Encantado" (In Search of the Enchanted Valley). As the characters were no longer looking for it in the sequels, that title was given the same treatment Indiana Jones (exemplified at the page top) was.
Stitch! The Movie, as a result of production issues. The movie was originally going to be titled Lilo & Stitch: A New Ohana, but then the decision was made to only have Stitch's name in the title of this and the subsequent series, which was going to be called Stitch! The Series. It was then decided to rename the series back to Lilo & Stitch: The Series, but the memo wasn't given to the marketing team for The Movie in time for the name to be changed.
Robot Chicken has a mild case in the new seasons. At first the premise is that the show is what the robot chicken was forced to watch. At the end of season 5 the chicken breaks free and beginning in the next season the show is what the scientist sees as payback from the chicken.
HiT Entertainment actually started out with an Artifact Title. The initials "H I T" originally stood for Henson International Television. During the first round of talks between Jim Henson and Disney in 1985, the management of the Henson international unit bought it out and made it into an independent production company. So by the time "HiT" started appearing on a Vanity Plate, it already had nothing to do with Henson.
After the first bunch of Popeye cartoons, the only thing that practically defined Popeye was his sailor outfit. This trope was sort of undone during World War II when he served in the Navy, but when Famous Studios took over production and the series switched to color, the "sailor" aspect was defined only by Popeye's white Navy suit. Some cartoons even had him with a totally different occupation.