Bubbles in Trailer Park Boys was originally just another supporting trailer park resident. By Season 2 he was a main character with Ricky and Julian.
Jimmy the Hand in the Riftwar series. Originally a one note character in the first book, he had his role expanded in the second and third. he was then the main character in both computer games, a one off book named after him and a complete triloogy of other books. Has been blatantly been placed as an expy (one of his own decendents) in pretty much every Riftwar novel since.
If we’re including TV shows and movies, I nominate Wolverine. I’m old enough to have bought the issue of Hulk where Wolverine was introduced, in a three-way-fight between Hulk, Wendigo, and Wolverine. Shortly thereafter, Wolverine was included in the roster of the new X-Men, and his popularity seemed to have never stopped increasing since then. I liked him well enough at first, but then he was written to be the ultimatest of ultimate bad-asses, that bar being raised again and again and again. I experienced a personal backlash for several years–anything I bought with Wolverine in it was only because of the other characters that were present and he just happened to be a part of that book. Once we got to the movies, I was more and more disgusted with how Wolverine was pushed to the forefront and basically became the star/leader (although I think Jackman has done fairly well with the role as presented). At the end of The Last Stand, where Logan strolls onto the balcony overlooking the schoolgrounds, looking over “his” domain–that was the most blatant image signifying (to me) that “I am The Wolverine, and I am the star of this franchise.”
But I could go on and on, so I’ll not. 
Inspector Jacques Clouseau in the Pink Panther series of movies: David Niven’s character was the lead in the first Pink Panther movie.
I remember The Simpsons being more about Bart until Homer broke out.
Ben Linus was supposed to be a brief, minor character in Lost, but he was so deliciously creepy and fans responded so well they made him a major character.
Walton Goggins as Boyd Crowder in Justified. He was supposed to die in the first episode, but test audiences loved him. I haven’t read the book (Elmore Leonard’s Pronto), but I think he was just a very minor character there.
P.G. Wodehouse’s Psmith started off as an eccentric supporting character to four-square schoolboy Mike Jackson, who originally headlined the stories. The flamboyant Psmith was so much more enjoyable than the bland Mike that in gradations of demotion Mike became the supporting character in *Psmith In the City *, had a couple of walk-on cameos in *Psmith, Journalist *, and by *Leave It To Psmith *had vanished almost completely. Also somebody please make a Psmith series starring Tom Hiddleston, who was born to play the genial and urbane trickster.
TV tropes must have a listing for this. Ah, they do.
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I think Will Turner was intended to be the lead along with Elizabeth. And they really are the main leads for the first 3 movies. Jack works way better as a screwball guy who they have to rely on. The fourth movie made him the lead and suffered. They should have made the missionary the lead character.
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Willow increased in power, but she was very far from taking over the show. The show is still hugely about Buffy through the 7th season.
Bart kind of was the first big thing. He had video games, the song, kids were wearing the underachiever shirts. As the show went on, they lowered Homer’s intelligence and competence and he got a lot funnier.
In the long strange history of the comic strip “Steve Roper and Mike Nomad”, this happened at least twice.
Ditto Aaron Paul. Jesse was supposed to die during the first season but his chemistry with Bryan Cranston made Vince Gilligan change his mind.
Dan Castellaneta is also on the record as saying Homer’s voice was originally based on Walter Matthau. Once Homer started to establish his own voice the real character emerged.
And now you know the rest of the story.
Australians with long memories will probably recall Sons and Daughters, a rather ridiculous 1980s soap opera based on a pair of star-crossed young lovers who later turn out to be long list twins, separated at birth. Their evil mother (“Pat the Rat”) soon became the focus of all of the storylines.
All of the other characters besides Ted in “How I Met Your Mother”. Ted is the titular “I”, but he’s the most boring character on the show.
Sawyer in “Lost” took over from Matthew Fox.
Yeah, but all the other characters were “mains” as well (they all appear on promo materials, opening jingle, etc). Kind of like in Seinfeld, Jerry was the “I”, but the 4 were all main characters.
In the early episodes of “Dallas”, the lead characters were good son Patrick Ewing and his new bride Pam. J.R. was their principle antagonist, but definitely secondary (or tertiary) in the plot to those two characters. Sue-Ellen was such a minor character that not only was she not identified as J.R.'s wife, she didn’t even have a proper name in the pilot script! She was simply called “Woman on Couch.”
On the 1960s daytime soap “Dark Shadows” was originally a “Jane Eyre” update, with prim & proper governess Victoria Winters becoming involved with the secretive Collins family. The single most famous character from the show -the vampire Barnabas Collins - didn’t show until a year into the run, and was supposed to be a short-term, ratings boosting gimmick. Actor Jonathan Frid was originally only signed to a 13 week contract.
On “General Hospital”, Luke (of the legendary Luke & Laura pairing) was likewise supposed to be a short-term villain who would be featured in a story line for about three months, then get killed off. But Luke became the central focus, and still is a major character, while Laura is long gone.
I seem to recall Popeye being introduced as a minor character in the comic strip Thimble Theatre.
A quick trip the Wikipedia article on Popeye confirms this:
A related thread on interesting secondary characters from 7 years ago that got zombied 2 years ago:
Secondary Characters More Interesting than the Primary Characters
The Hobbit and The Lord of the Rings.
Bilbo was the principle character of the first book, but was greatly marginalized, in favor of Frodo, Gandalf, Aragorn, anyone really.