The Chipettes from Alvin and the Chipmunks. After their first appearance in the '80s cartoon, they have become so popular and get more and more screentime overtime in the series becoming regular characters. Now the Chipettes are integral part of the franchise and appear in all media.
Roger from American Dad! originally started out as an alien who lives with the Smith family as well as being forced to stay within the house and didn't have much major importance to the plot. Later in the series, he was more outgoing through the use of disguises and is one of the more prominent characters. Recently, he's the second most prominent character after Stan, and is now one of the most popular characters on the show.
While Animaniacs was always intended to be a series of shorts with many different characters, the incredible popularity of the Pinky and the Brain shorts led to them appearing in significantly more episodes than the other skits. They were also the only ones to spin-off into their own show.
Pam wasn't even in the opening credits on the beginning, but she quickly became a fan favorite from Season 1 to 4, season 5 however, made her The Scrappy, as she held the Idiot Ball and didn't let go, her addiction on cocaine became an Overused Running Gag in the season and even lost her Big Beautiful Woman attributes for a typical Statuesque Stunner. She came back to being a main character with her old personality by Season 6.
Krieger and Ray were side characters with almost very few lines in Season 1, the creator voiced Ray in order to save money on voice acting since he was supposed to be a one-off character, but both became so popular they were added to the main crew.
Bob's Burgers: Tina, the awkward teenage girl who writes erotic fanfiction, likes horses and zombies. Her awkward adorableness as well as her self-confidence in being herself and relatable teenage issues made her become very popular and one of the most focused characters later in the show.
Donald Duck upon his second appearance, (and his first on a Mickey Mouse cartoon) where he effortlessly steals the picture away from everyone. It wasn't long before he became much more prominent on the cartoons than the Mouse himself, before serving as a the centerpiece for an entire comic book universe that is overwhelmingly adored in Europe. Walt Disney is on record as saying that he never quite understood why people became so attached to the character.
Shego from Kim Possible started out as a flat sidekick to Dr. Drakken. Her portrayal by voice actress Nicole Sullivan had the creators add more depth to the character, and her dynamic with Dr. Drakken became so popular that the duo became the most featured (and fleshed out) villains in the series.
Thumper proved an endearing foil to Bambi and for a long while Disney considered giving him his own spin off movie. While this never came to be (yet), he still appears on as much merchandise as Bambi himself and even has his own separate toy and storybook line, Disney's Bunnies.
Marie from The Aristocats (also mentioned in the Animated Films on the main page) quickly became a very beloved character by the company. Previously Thomas O'Malley and The Scat Cats served as Disney's choice to represent the film. Disney quickly picked Marie as the character to represent the film. Beginning in the early 1990s, Marie became Disney's answer to Hello Kitty and attempted on giving her animated starring rolestwice . note The first was "The Aristocats: The Animated Series" were Marie, alongside Toulouse and Berlioz were the main characters. The second was "The Aristocats II" where Marie was the main protagonist. Currently Marie stars in tons of Aristocats related books, merchandise, a manga, and is insanely popular in Japan and Brazil. As a result of Marie's popularity, The Aristocats is the only Disney Animated Film from the 1970s that's frequently used in merchandise and other Disney related works.
Phineas and Ferb had Perry the Platypus, the title characters' pet, and a secret agent, and Dr. Doofenshmirtz, one of the most pathetic villains ever created. It soon got to the point where Doofenshmirtz's plotlines with Perry pretty much usurped the title characters' plotline. Perry himself even got acquainted with Disney's merchandising, like in Disney Tsum Tsum.
Felix the Cat was originally conceived as a One-Shot Character for the film Feline Follies, which was made solely because another animator was tardy with his work for the Paramount Screen Magazine, and Pat Sullivan and Otto Messmer agreed to fill in with a cartoon of their own. Felix's debut was so well liked by audiences that it immediately took off as a hit, graduated to his own standalone series and became one of the most iconic and influential cartoon characters of all time.
Snagglepuss originated as a recurring antagonist in various Hanna-Barbera shorts, but somewhere along the line he ended up with his own series of shorts (backing up Yogi's own show) with him as a heroic character, and his endearing personality and mannerisms meant that he ended up becoming just as enduring of a cast member as Yogi.
Among the company's many Scooby-Doo clones produced during the late 70s/early 80s, Jabberjaw remains one of the most well-known and popular of them, to the point that he transcended his own origins as the main character of a Scooby clone and routinely makes appearances in other Hanna-Barbera shows and movies (even ones that don't have anything to do with mysteries), even having a supporting role planned for SCOOB!* as a female interpretation of the character before it was cut for time.
I Am Weasel started out as a supporting cartoon to help complement Cow and Chicken, in same vein as Dexter's Laboratory's "Justice Friends" and "Dial M for Monkey". The characters of Weasel and Baboon were loved enough that the shorts were eventually spun off into an independent series.
GIR in Invader Zim. He is certainly the favorite among the majority of fans, though his voice actor is annoyed when fans ask him to do something like sing the Doom song due to doing the voice straining his throat. And aside from that, Nickelodeon still makes lots of GIR-themed merchandise, and now they've reached the point where they have to make up new quotes just to put on T-shirts. Remarked on in the script reading for unproduced episode The Trial.
"Back on Earth, mankind has reconstructed the planet. Everything is in GIR's image." Richard Horvitz: Just like Hot Topic!
Porky Pig: The original breakout character. He was intended to be a sidekick to the much-forgotten Beans the Cat. Originally appearing in 1935's I Haven't Got a Hat, Porky proved much more popular than Beans, causing him (along with the rest of his co-stars) to be written out within just one year, while Porky remained prominent for decades to come. However, he was eventually upstaged by...
Daffy Duck: First appearing in 1937's Porky's Duck Hunt, Daffy was merely one of the many ducks Porky was hunting. However, he would end becoming even more popular than Porky himself, soon starring in a series of his own shorts. But much like Porky, Daffy would end up being upstaged by...
Bugs Bunny: Bugs made his debut in 1940's A Wild Hare (though, his prototype (Happy Rabbit) first appeared in 1938's Porky's Hare Hunt). With his Karmic Trickster personality, he quickly became the franchise's most popular character, and remains the face of Looney Tunes today.
Foghorn Leghorn: Originally a supporting character to Henery Hawk who debuted in 1946's Walky Talky Hawk, Foghorn proved more popular to the point he became the main star of his shorts, with Henery as the supporting character instead.
Marvin the Martian: Though he only appeared in 5 Golden Age-era shorts (starting with 1948's "Haredevil Hare"), Marvin became much more popular after the official run, appearing on much of the merchandising, alongside the main characters.
Tasmanian Devil: Like Marvin, Taz only appeared in 5 Golden Age-era shorts (starting with 1954's "Devil May Hare"), but also became much more popular later on through merchandising and even getting his on show in the form of Taz-Mania. It may come to as a surprise to some fans that Marvin and Taz only appeared in 5 of the original shorts.
Michigan J. Frog. He appeared in exactly only one cartoon — "One Froggy Evening", yet he endeared himself to audiences so much that they convinced himself he appeared more than once. In the 1990's he eventually became one of the starring characters when he came the mascot for The WB Network.
Luna Loud started off as just one of Lincoln's sisters. However, she quickly gained a ton of fans, and subsequently became the sister with the most episodes that focus on her, including a special.
Ronnie Anne became popular when she has formally introduced in "Save The Date" thanks to emphasizing how she's tough yet also has a good heart while also showing her more lovable behavior. Once she moved to the big city to live with her mother's extended family, she became more popular, and eventually got a whole 5 episode arc in season 4, and her own show.
Metalocalypse: Charles Foster Ofdensen wasn't even in the first episode and remained a relatively minor character for the first few episodes of the show, but slowly became not only a great straight-man foil for the band but became an incredibly popular character in his own right as well as a genuine member of the main cast, leading up to several spotlight moments in Season 2 and culminating in his Heroic Sacrifice at the very end of the S2 finale. He gets better.
Princess Luna, sans her time as Nightmare Moon, was only in the series premiere for only a mention in the opening narration, less than a minute of screentime, and two lines before being absent and unmentioned the rest of the season. She proved very popular with her focus episode "Luna Eclipsed" furthered while it and a two cameos in the season finale were her only appearances in Season 2. From Season 3 onwards she would get almost as much screentime and prominence as Princess Celestia, getting Promotion to Opening Titles in Season 4.
Discord first appeared as the Big Bad of the two-parter "Return of Harmony" as essentially a chimeric version of Q, and was so awesome that many fans couldn't help but fall in love with him. Although Taken for Granite at the end of his debut, he was revived in season 3 to be successfully redeemed (of sorts) by Fluttershy and was promoted to recurring character in season 4. Hes proven popular enough to receive a supporting role in pony life.
The Great and Powerful Trixie only had one appearance in season 1, which made her extremely popular. She would only return in the season 3 episode "Magic Duel", to further acclaim. Season 6 has her become friends with Starlight Glimmer (who, at this point, has been promoted to full-on main character), which leads to her getting more appearances.
Rugrats: By the last few seasons, Angelica Pickles became the most popular character of the franchise. She was the only Rugrats character to make TV Guide's list of Top 50 Greatest Cartoon Characters in 2002, and she and Susie also got their own short-lived spinoff Preschool Daze.
Timmy in South Park was initially intended as a one-shot character, but proved so popular (spawning a Memetic Mutation, TIMMY!) that he was brought back again and again, and even made it into the opening in the sixth season, after the departure of Kenny. However, after his brief moment in the sun, he quickly receded into the background again.
SpongeBob SquarePants: Patrick basically stole the show in the earlier episodes, that he eventually got tons of episodes centered around him. For most of the SpongeBob memes out there, Patrick has spawned the most out of the other characters.(e.g. The Ugly Barnacle, Surprised Patrick)
Star Wars: The Clone Wars: The clones of Domino Squad were originally created as one-shot characters for the episode "Rookies". However, due to the episode and the squad proving so popular among fans, season 3 started with a flashback episode showing their backstory. Fives and Echo, the only surviving members of the squad, became recurring characters with their own subplot from that season onwards, with Fives eventually serving as the main character of the Order 66 arc, and Echo becoming one of the leads in Star Wars: The Bad Batch.
Dave Filoni: On the crew, ["Rookies"] was one of our favorite episodes. When it aired, it became very clear that the fans also really related to the rookies, they really liked that episode, and we thought: "Wow, we've really got something here."
Courtney is another major example. She's not quite part of the main crowd at first and gets eliminated about halfway through the first season. At this point, she was mainly known for being Duncans Love Interest, a Nice Girl (as a case of Early Installment Weirdness from the first few episodes), and a minor foil to Heather for basically filling the role of Alpha Bitch on the opposing team, albeit a far kinder and more sympathetic version than Heather. She doesnt even qualify for Season 2! This all changes when she makes a surprise return as the Big Bad halfway into Season 2. From there, she returned in Season 3 to get involved in a messy Love Triangle with Duncan and Gwen and her popularity skyrocketed from there, thanks to both fans (those who sympathized with her for being cheated on) AND haters (those who thought she was unnecessarily cruel to Gwen) developing strong emotions for the character one way or another. By the time Season 5, All-Stars, came around, her immense popularity made her an easy pick. By this point shes considered one of the faces of the series, and also a member of Total DramaRamas Spot Light Stealing Squad.
One of the back-up segments on Underdog was Go Go Gophers. This segment was so popular it became its own show, albeit only consisting of reruns from its days on Underdog.
Woody Woodpecker: Woody first debuted in the Andy Panda short "Knock Knock" but ended up becoming so popular that he immediately spawned his own series of shorts, quickly eclipsing the cute little panda in popularity.
In a somewhat meta-example, WordGirl originated as one of many shorts and interstitials attached to the second half of Maya & Miguel. The WordGirl shorts wound up popular enough to get their own show, and has since outlasted the largely forgotten Maya & Miguel.
Xiaolin Showdown: Raimundo pretty much stole the show from Omi, being the character with the most development, and ended up supplanting him as the main character by the finale.