Ghostopolis: Skinny starts out as Garth's sole companion, but then gets pushed to the sidelines until the end of the story.
Despite being the reason for the League of Extraordinary Gentlemen's existance, and being the driving force behind the plot of the Black Dossier, Prospero disappears almost entirely, and only makes an appearance during the last chapter of Century to get Orlando to resume her search for the Moonchild, and disappears entirerly after that, not even supporting the remnants of the League during the final battle.
In Paperinik New Adventures all the important supporting cast of Donald Duck (Uncle Scrooge, his nephews, Daisy) were reduced to background characters or cameos to make place to new characters.
This happens to the main cast in Sibylline, after the series creator Raymond Macherot neared the peak of his Creator Breakdown. In many of the later stories, Sibylline and her friends got far less panel time in favor of the villains and their self-inflicted failings, to the point that the former often never interacted with some of the latter, let alone dealt with them. Luckily, this got fixed after the series got a revival.
This happens in Sin City, mostly because different stories have different protagonists. For instance, Marv was the main character in the first story and a supporting character in the second. Aside from two one-shots, he was never the main character for any stories after that. Later stories have him showing up as an extra in the background (often if the scene takes place at Kadie's Bar) with one or two lines. Word of God states that he will be the focal point in future tales.
Rotor Walrus in Sonic the Hedgehog, both SatAM and Archie Comics versions, have been hit hard with this; in both versions, he started out as a strong fixture in the Freedom Fighters, then got kicked into this position after a certain point (Season 2 in SatAM, issue #125 in the Archie Comics); in fact, in the comics, his jacked-up importance and Word of Gay relationship in the "Mobius: 25 Years Later" storyline was meant by previous head writer Ken Penders as a way of moving him out of extra status and giving him a much-needed jolt of Character Development. Sadly, when head writer Ian Flynn took over, he was beaten back down to this spot violently, in both the main comic and the "M:25YL" storyline for quite some time. He eventually regained some prominence when he joined the Royal Council and later made himself a high-tech suit, but not until he'd been largely unseen for several years.
A group of characters called "The Substitute Freedom Fighters" faded out of relevance soon after their introduction. They were brought back as councilors on the royal council. One of them, Hamlin, was angry enough about his treatment that he joined the council out of spite for the Freedom Fighters.
Knuckles has also been demoted heavily since his own spin off comic series ended, likely due to his life on Angel Island making it harder to focus alongside the Freedom Fighters down on Mobius.
Interestingly, Sonic himself was affected by this - after the Knuckles comic got cancelled, Sonic was limited to mostly being stuck in Knothole following the Sonic Adventure adaptation, with Knuckles and Tails getting a lot of the screen time and action in their backup stories, due to a case of Creator's Pet.
In Tomorrow Stories, Greyshirt's sidekick, Rocky, barely appears in Indigo Sunset at all.
The Transformers Megaseries: Soundwave was taken out of action twenty-odd years ago, and spends most of the run stuck in tape-deck mode.
Transformers: More than Meets the Eye: While the other four Headmasters all have story lines, with Hardhead's in RID, Highbrow has been pushed to the back.
The Authority: The Carrier, the Authority's sentient massive spaceship, started as a pseudo-relevant character with a mysterious past and a lot of atention was given to both the dimensions it travelled through and its friendship with the Authority. Since Jenny Sparks' death, however, The Carrier wasn't given much atention, only being used as a base and as a teleporter.
Turma da Mônica e Garfield: O Lápis Mágico: Despite Jon, Arlene and Nermal being main characters in the Garfield strip, they are not in Vol. 1 despite being present on the cover. They do appear in Vol. 2 to give Garfield and Monica's friends hints about where Captain Fray and the lasagna monster were, but that's it.
Usagi Yojimbo has Lord Hikiji, who killed Lord Mifune and Usagi's father, causing him to become a Rōnin and thus kickstarting the entire plot. One would think he'd be the important Big Bad, but even early on, the bulk of screen time went to Lord Hebi...and then came Jei-san, whose immense popularity propelled him to Arch-Enemy status and finalized Hikiji's demotion.
