Adventure Time. The majority of the cast includes one episode appearances like Penny and background characters like Lollipop Girl and Gumdrop Lass. The show also had the distinction of nearly doubling the entire cast in just one episode; "Fionna and Cake", in which the main cast and Candy Kingdom residents were all genderbent.
The Animals of Farthing Wood has a long list of characters at the beginning of the show. Many more get introduced as the series progresses, but only a handful of the original cast survives the series. (everybody else has died due to cold, old age, hunters, producers who just cut them out of the show without a single explanation, etc.) The survivors are Fox, Weasel, the Rabbits, Owl, the Squirrels, and Toad.
DuckTales (1987) and its 2017 reboot are shows well known for their massive cast of major and recurring characters. Scrooge McDuck is a duck who has many friends, employees, and tons of sworn enemies, not to mention many Duck/McDuck family members who either live with him or visit him.
Wikipedia contains expansive entries for forty named characters in Exo Squad, nine of them in The Squad alone. And they are not being particularly thorough at that...
The Fairly OddParents!. Seriously, how can kids keep track of all those characters!? Just check out its character page on That Other Wiki. It's even got a subcategory for inanimate objects. Phillip the nickel, that rock in one episode that was more popular than Timmy...
Family Guy has at least 30-50 characters considered either major or recurring.
Futurama, to the point where one of the last shots of the final DVD Movie was a massive crowd shot featuring every character except the children (to keep continuity with a line that stated they weren't there) purely as a fan-pleaser.
In one of the DVD commentaries, someone wonders what it would be like to have a machine that can mimic every character's voice, to which someone else replied "We do, it's called Billy West."
Gargoyles helped keep track of additional characters through a Cast Herd; everyone is connected through their primary associations. Of the main characters there is Goliath, Hudson, Brooklyn, Broadway, Lexington, Bronx, and Elisa; with Xanatos and Fox being second only to them. Then there are individuals like Matt Bluestone, Macbeth, and Demona. After that there are the various groups like The Pack, the Mutates, the Hunters, the Avalon clan, and the magical creatures like Puck, Oberon, and Titania. And then there are the characters that are the lesser seen including the England clan and family members that show up like Elisa's family, Fox's father, and Xanatos' dad.
Handy Manny focuses on quite a lot of the residents of Sheet Rock Hills. In fact, there are ten main characters: Manny, Kelly, and the tools.
Justice League started with a core cast of seven heroes, and a handful of recurring villains. Starting with the third season, they make it a true league, and at one point state that they have at least sixty members (not counting a few rogue agents like Huntress and Hawkman), plus the villains, plus two of the Cadmus folk. This meant that at the very least, these characters would be seen in the background in the Watchtower, or in fights, and several got moments to shine.
Super Friends also started with just a core cast, but continued to add more heroes (and villains) each season.
The aptly named Legion of Super-Heroes is the same idea applied to the DCU as seen in the 31st century. Its format, however, tends to be "the core plus one or two guest members", with larger numbers turning out for major threats.
Laff-A-Lympics was a spoof of the "trash sport" TV specials which featured 45 Hanna-Barbera cartoon stars as participants plus two as on-field commentators (Snagglepuss and Mildew Wolf) and cameos from numerous other HB characters.
To start with, there are the "Mane 6+1" primary characters: Twilight Sparkle, Fluttershy, Rainbow Dash, Rarity, Applejack, Pinkie Pie, and Spike.
After that, there are the Cutie Mark Crusaders: Sweetie Belle, Scootaloo, and Apple Bloom.
Following them are the Princesses: Princess Celestia, Princess Luna, and Princess Cadance.
Then we have the Apple Family regulars: Granny Smith and Big Macintosh.
Slightly behind them are the Wonderbolts, mainly: Spitfire, Soarin, and Fleetfoot.
Add to that a large number of major recurring characters and villains: Discord, Cheerilee, Shining Armor, Zecora, Mayor Mare, The Great and Powerful Trixie Lulamoon, Lotus Blossom and Aloe (the "spa ponies"), Maud Pie, Mr. and Mrs. Cake with their foals Pumpkin Cake and Pound Cake, Diamond Tiara, Silver Spoon, Snips, Snails, Featherweight, Pisqueak, Flim and Flam, Braeburn, Babs Seed, Donut Joe, Bulk Biceps, Hayseed Turnip Truck, Steven Magnet, Starlight Glimmer, Gilda, and fan-favorite Derpy Hooves aka "Muffins". And, of course, many more minor recurring characters, and recurring background character; with a lot of one-shot characters showing up here and there (some of whom get brought back later to become recurring characters).
With the Equestria Girls spinoff, there aren't as many recurring characters; but more continue to be added. At this time there are the same Mane 6 (aka "HuMane 6"); Spike; the three princesses, now Principal Celestia, Vice-Principal Luna, and Dean Cadance; Sunset Shimmer; Flash Sentry; and Trixie Lulamoon. A number of other characters from Friendship is Magic also cross over, but typically have only very minor or non-speaking background roles, although some show up as major characters in the short prequel videos. Vinyl Scratch aka DJ Pon-3 is arguably a major recurring character, despite never actually speaking. So far, aside from Sunset Shimmer and EQG-universe Twilight Sparkle, none of the villains have become recurring characters.
Due to its long run, the number of characters in The Simpsons that could be considered regular is at least 30-50, possibly even more.
There is a poster that actually lists the characters that have had more than one episode, and it was well over 100. There are even T-shirts◊ of this (though this one is almost 10 years old, and enough characters have been introduced since then to fill another t-shirt size crowd shot.)
South Park has loads of characters, too. Anyone who's had at least one episode focused on them can be considered a main character and that's at least a good 25 - 50 characters right there.
The Spectacular Spider-Man has the obvious ones, Spidey, Gwen, MJ, Aunt May, Norman Osborn, Harry Osborn, JJJ... and then there's three cops, four co-workers at the Daily Bugle, and eight or nine other people at Midtown High School, and that's not counting the seventeen supervillains and at least five future supervillains.
Star Wars: The Clone Wars doesn't really have a regular cast aside from the obvious Obi-Wan, Anakin, and Ahsoka trio; with Captain Rex, R2-D2 and Padmé as notable recurrers; and C-3PO and Cody occasionally thrown into the mix. Then we still have fourteen Jedi, at least ten Republic military officers (both clones and non-clones), six Separatist officers, six bounty hunters, and seventeen non-aligned characters that have important roles in more than one episode. There's also a huge horde of about fifty one- and two-shot characters.
Star Wars Rebels quickly followed in The Clone Wars' footsteps. As of the end of season 3, there are, besides the six main characters, five rebels, thirteen Imperials, and four criminals who've been in notable recurring roles. This is not to mention several significant characters carried over from The Clone Wars, as well as a large number of one- and two-shot characters.
Star Wars Resistance, by the end of the first season, besides the five main characters original to the show, introduced no less than 21 characters, original to the series, who are in some way significant. There are also four movie characters in recurring or regular roles. Again, this is all in its first season, not mentioning the large crowd of Recurring Extras that populate the Colossus in the background.
Steven Universe started with a small cast but slowly introduced characters as the series went on, with both the named humans and Gems growing in number. Continuity Creep gave multiple town residents and their families A Day in the Limelight, while the new Gems started out being introduced at a rough rate of one every half-season (Lapis, Peridot, and Jasper) until being seen in droves around Season 4. The latter is because the Gems on Earth are the last un-corrupted of their kind, while Homeworld still has a massive population. As Homeworld becomes more relevant to the story, more of their units show up. What started with just four Gems and two donut shop employees from the first episode turned into the population of a small town and the various factions of a huge galactic empire.
Aside from characters from the aforementioned series, pick out any popular Marvel character and it's a good chance they're on The Super Hero Squad Show.
Teen Titans' final season has the team meeting up with other young heroes, typically having one main Titan defending one or more less experienced members from villains. It's a good thing, too, since nearly every villain in the show's history, down to even long-unseen one-shot villains (but excluding most Big Bads) had also teamed up. It all comes together in a two-episode Final Battle. Even being dead when last seen was no excuse for a hero or a villain to not be in on that one.
Seasons 1 through 4 though don't particularly follow this trope: there's 5-8 major cast members and maybe a dozen recurrers.
The Venture Bros. has Team Venture itself, the Monarch and Dr. Girlfriend, the Monarch henchmen, the Guild of Calamitous Intent, OSI, the Order of the Triad, the original Team Venture, and dozens of other supporting characters.
Voltron: Legendary Defender: Aside from the six core characters, there's also the original Paladins, various officials of the Galra Empire, the Holt family, the Kogane family, everyone else's families, the Blade of Marmora, Lotor's generals, various members of the Voltron coalition, multiple Alteans, and all the crew members of the Atlas.note There is some overlap between these groups
Much like Laff-A-Lympics that would come nine years later, Wacky Races featured 22 individual characters in eleven separate vehicles.
That's not even counting the as-of-yet unrevealed kids who joined the team during the five year Time Skip, like Robin II, Aquagirl, and Tempest.
By co-creator Greg Weisman's own count, 179 DC "named" characters were used in season one (though a few were cut for time and such). 145 appear in season two.
Outsiders continues the trend. You have the Outsiders (which include Ascended Extra Black Lightning and newcomers Halo, Geo-Force, Forager and Cyborg) themselves, the third iteration of the Team, the Justice League, Batman Incorporated (Batman's splinter faction that includes Green Arrow, Robin III, Batwoman, Arrowette, Hardware, Plastic Man, Katana, Metamorpho, Spoiler and Orphan) The Light, and various other villains, heroes, and side characters, all while adding new members to the already crowded cast.