One of the rules of fanfiction is anyone can be the main character, even if they had three seconds of screentime in the source material.
In the X-Men fanfic Mutatis Mutandis, the author mentions that initially Jean-Paul was supposed to be Rogue's snarky best friend and moral compass but realized he was described in a way that did not lend himself to such a role. Thus, Victor (Anole) became the blue oni to Anna's red.
Luminosity diverges from the plot of the Twilight novels radically enough that this is almost a guarantee. One notable example would be Gianna, whom Twilight fans would know as that woman who was in the Volturi's waiting room and whom Luminosity fans would immediately recognize—her brother Ilario gets a role, she's Elspeth's mother, she's Maggie's mate...
Ever since Blaise Zabini shared a train compartment with Draco, he's shown up in countless fanfics as Draco's BFF. This is particularly noticeable when authors fail to get the few facts we do know about him, such as his dark skin or the fact that his mother has married seven times (with a very strong implication that she's a Black Widow).
ThisDeath Note fanfic does this with Matt, who went from One-Scene Wonder of 16-panel and 30-second fame in canon to becoming one of the main characters. In fact, L needs him specifically to not only solve the Kira investigation, but also to resolve the tension between Near and Mello.
And then there's Lindanote A literal One-Scene Wonder who doesn't even appear in the anime, who also seems to be a central character. though as of late she's been Put on a Bus.
Winter War has a lot of these, ranging from Minor Major Characterss like Sasakibe, who goes from "the Lieutenant of First Division who never does anything" to a more fleshed-out character and a mainstay of La Résistance, to characters who had brief importance in canon and haven't been seen since (Shiba Kuukaku, Rikichi, Inoue Sora) and become pivotal again in the fic, to Omake characters like Shirogane and Ogidou getting personalities and plot importance, to literal Ascended Extras like Ito- who seems to be the nameless guy with the blond mohawk in the Eleventh Division ending of the anime.
Lily from Pokemon Mystery Dungeon Silver Resistance. First she was submitted as a potential character for the prequel, Emerald Chronicles. After that, she starts appearing in the main story, eventually joining the main characters on their quest.
Eris Game makes Eri, Shiki's best friend, the main character and narrator of this fanfic.
The Deliver Us From Evil Series gives a veritable host of Ascended Extras from the Sherlock HolmesCanon. The first novel alone has Inspector Patterson, from one mention in "The Final Problem" to full supporting character status; Wiggins, from two brief scenes in the first two Sherlock Holmes novels to another supporting character; Inspector Lestrade, from recurring character to Deuteragonist (one of the leading points-of-view in the novel); Mary Watson and Mrs. Hudson, from recurring extras to supporting characters. Moriarty and Moran also get a lot of screen-time, and Culverton Smith has a bigger status as the villain for the first quarter of the novel.
The Road to Reichenbach is meant to be starring several Scotland Yarders from the Canon, and these characters should maintain their prominent status throughout the rest of the series.
To Take Up the Pen, the future third novel in the series, will up the ante further with Colonel Moriarty, a character who receives only one clear mention in the Canon, and Colonel Hayter, a One-Scene Wonder from one of the short stories. Also, Colonel Moran (yes, that's a lot of colonels, but they're all canonical) ascends to Big Bad status as he chases Holmes across Europe and Asia.
Game Theory has quite a few. Tiida Lanster, Quint Nakajima, Megane Alpine, Linith, and Nanoha's mother were all fairly minor characters in canon, but they've been given significantly expanded roles in this story. But the most prominent example is Vesta, who was just a nameless kitten in the original work. In Game Theory she becomes Nanoha's familiar.
Not to mention Alicia Testarossa in the sequel.
In No Hoper, a Death Note and The House of NightCrossover, Kayla becomes a proper character again. Also Yamamoto-Light's friend from school who appears in a few pages of the manga and doesn't appear in the anime-is one of the few other characters that makes a showing from Death Note canon. As for from The House of Night canon, Drew Partain - who'd only gotten a couple of mentions as Stevie Rae's maybe boyfriend in the books - and 'Amanda', who only ever had one mention in the first book.
The Legacy Of The Blood Ravens expands the roles of characters that are only mentioned or have few lines. Oddly enough, this is even the case for the Force Commander Aramus, who has no lines in the games themselves.
The Suite Life On Deck story "Life Unexpected" uses Reina, who appeared in exactly one episode as the antagonist, becomes Bailey's best friend and even given a developed backstory making her the child of a teen pregnancy. This was the main driving force behind their friendship as she sympathized was Bailey who was pregnant.
In general Suite Life fanfiction this is true of the character of Max, who appeared in only six episodes of the very long series. Partially due to being played Alyson Stoner, partially due to her Deadpan Snarker nature, and partially due to being more bearable than Girl of the Week Zack was with.
The Sherlock Holmes/Doctor Who crossover Children Of Time features Sally Sparrow, the heroine of "Blink" in a prominent role. After the series' AU of "Blink", she marries Dr. Watson (her co-star in said AU) and becomes the Cool Big Sis to Beth Lestrade as well as the Team Mom to the Irregulars. And that's not even mentioning the baby...!
Val for The Wall after Jon Snow's death at the hands of his brothers.
Jeyne Westerling for Greywater Watch and eventually White Harbour.
Sandor Clegane for the Riverlands and King's Landing where he hopes to kill off his undead brother.
Ramsay Bolton for Winterfell after Theon Greyjoy escaped with Jeyne Poole.
Willas Tyrell for Highgarden.
A Growing Affection makes Yugao Uzuki a major supporting character. She has a romantic subplot, gets her own team, and gets a Back Story linking her to Anko and Iruka. Who also appear in a more pivotal role in this story.
The Vampire Diaries fanfic Love Bites, So Do I does this was with Tina and Blair, two minor characters from one episode who had one line a piece. although recasted, they are made into the main character's older sisters while Tina dates Damon before having a baby with Matt and Blair is actually a werewolf. Later chapters use Valerie Fell, who has NO lines and appeared for all of 3 seconds at most.
In the DiscworldExpanded Universe of author A.A. Pessimal, Ascended Extras who may be no more than throwaway names and non-speaking one-line spear-carriers in Canon become rounded-out central characters alongside the established cast. some, like Howondalandian Assassin Johanna Smith-Rhodes have become stars in their own right; a recurring line in reviews by fans is that they can't see the join where Pratchett ends and Pessimal begins.
In Mega Man ZX Enforcers, Biometal Model O, a non-canon "bonus" Biometal in the first ZX game, is stated as having been stolen from the Guardians alongside Models F, L, H, and P (thus technically making Vent and Aile's acquisition of it canon by this story's standards), but had no Biomatch and was thrown out. Model O is now used by Taylor, a new main character. Model O actually speaks in this story, but is FAR calmer than the Reploid he's based on.