In the comments on this page of 151 Hidden Depths.
"And Hitmonchan is definitely his own character now. Seems like just yesterday I only used him to fill out a bully spot with no future plans on what to do with him..."
In the sprite comic Ansem Retort, Red XIII was initially a member of the replacement cast while the main cast went missing. Thanks to some manipulation by Darth Maul, he became evil enough to fit in with the main cast. His ascension was complete when the rest of the cast picked him over Marluxia to come along on a trip to Hawaii.
And in the newest season, Marluxia is actually trying to reverse his demotion to extra. This is why he won't let Sora be taken hostage: he gets more screen time this way.
Jason Porter from Domain Tnemrot. In volume one he's just the guy who riles up the crowd during the titular stadium's matches and wasn't even important enough to get a name beyond 'Ref' but then in volume two was upgraded to be a major antagonist. His tag is still 'ref' though.
The Fourth, the demon minion Davis, fist appearing in a shoddy dungeon Lord Skava the Fourth joins Skava Manor after his dungeon is put out of business
In El Goonish Shive, Rhoda was previously just another of Diane's lackeys and not more than a minor character. After her character was merged with that of an extra, she became more of a supporting character and her actions kicked off a major storyline albeit without her knowledge.
Susan was also just going to be Sarah's friend and head of Moperville North's Feminist Club, but not much else. Fans declared that she looked perpetually bored, but Dan said that, as he fleshed out Susan's character, the half-lidded eyes that Susan sported reminded him of something other than boredom.
Kiley Shefford entered Ménage ā 3 as a one-panel gag; a nameless sufferer from the A-Cup Angst so often induced in other women by the sight of DiDi. She subsequently reappeared looking after a magazine stand visited by Yuki, who vandalised some of the stock. Kiley promptly volunteered to act as Yuki's psychotherapist, with some mixed success — which in turn led to her deflowering Gary, the comic's original protagonist, whose virginity was widely assumed to be the comic's prime concern. Kiley later returned as Matt's lover, friend, and therapist, and continued to work with Yuki. And she's still working on the A-Cup Angst.
Peggy may also have the look of a former extra, although her ascension was meteoric, from panel-side joke to only (relatively) sane woman in half-a-dozen strips.
MS Paint Masterpieces: AllMost of the Robot Masters get bigger roles than they did in the original games, but Electric Man got this the most.
Daigo and Kazumi Kato. Their progression from Red Shirts to Mauve Shirts is lampshaded when they invoke the trope Nominal Importance, and they continue to gain importance from there, both in-universe (being risen to nobility) and in the narrative.
Celia's case is especially glorious, beginning as a mere gate guardian NPC and ending up as the main character's girlfriend.
V's Familiar, Blackwing, started as a minor character who only appeared in order to be involved in jokes about spellcasters who neglected or misused their familiars. Then he became a Chekhov's Gunman when he played a crucial role in a plan cooked up by O-Chul and V, and has since become a member of the main cast.
Kathryn in Schlock Mercenary. Most of the main cast has explicit ties to the toughs. She just won't go away.
In Sinfest, the anonymous succubi who hung onto Satan's arms turned into Fuchsia, a Love Interest and immensely popular character, and Baby Blue, who got less development but did acquire a name and a friendship with Fuchsia, fueling conflicting loyalties for her. Even the green succubus, introduced after Fuchsia left Satan's employment, has more characterization that the masses of succubi before.
Dr. Schlock entered Sluggy Freelance as a one-off Chew Toy for Bun-bun's ire. His time-travel counterpart became involved in more and more major story arcs, until he got one of his own arc plus a major hand every other.
In Suppression, Kirk started out as a random mook that got punched in the face by Sally.
When Andrew was working on Problem Sleuth, he was accepting donations for non-canon fan commands in the secrets page. One of those commands was Problem Sleuth summoning The Midnight Crew. A few more commands later each member were given actual names. They then became a recurring canon element of Homestuck before later properly debuting as full-fledged characters in an intermission, and have gone on to sporadically appear since then. In fact, a direct Alternate UniverseExpy of the Crew's leader is Homestuck's Big Bad.
After the Scratch, the kids' various ancestors step into the spotlight and join the main cast. Pretty good for faceless characters that Hussie didn't even originally know would all be ancestors.
Lil' Cal goes from being a creepy joke prop to being the ectobiological father of Doc Scratch to being Lord English's host. And then it's revealed that he's something called a "juju", which apparently brings calamity to all universes it has ever existed in.
GamzeeMakara was one of the least notable trolls... until he ran out of sopor pie and went Ax-Crazy. Also, he created Lil' Cal, and was the surrogate father to the Big Bad!
in Voodoo Walrus a couple of lowly union ninjas by the name of Phil and Dave go from being sources of amusing random conversation (usually regarding one's problematic ex-girlfriend)to Mac's personal right-hand men in the Infernum slaughter. Though the ex-girlfriend commentary still lingers.
NUXXOR! also went from being a random, expendable extra to a prominent villain later on.
In Wapsi Square, Tina was originally a minor, recurring character who ran the coffee shop the main characters frequented. However, once the strip's supernatural elements started to become more prominent, she developed a bizarre backstory and effectively became a main character in her own right.
YU+ME: dream has Lia, who pretty much intruded into Fi's dreamspace. Also, from a slightly more straightforward perspective, Lia's "cousin" Sadako.
Once a minor character in The Word Weary, Mona Byrnewald has ingratiated herself into the main story and become one of its most integral parts.