Finn and Flame Princess have a romance, and they really try to make it work, despite her being made of fire and thus physically unable to touch Finn without burning him, but eventually, they break up.
Tree Trunks and Pig are a downplayed version. Everyone just finds them kissing in public gross, and spend a part of one episode keeping them apart.
American Dragon: Jake Long features a romance between a dragon and a girl raised by a family of dragon-slayers. Think of it as Romeo and Juliet, except they don't kill themselves, they try to kill each other. She gets better, though.
Amphibia: Played with. Anne Boonchuy and Sprig are not in love with each other (not to mention the disturbing implications that might bring), but they have an incredibly strong friendship and dread the thought of parting ways. Anne is from Earth, which means that she must eventually leave Amphibia and Sprig behind. Throughout the series, while Anne wants to return home, a part of her still wants to stay with Sprig forever. In the Grand Finale, they must return to their different worlds, but they both keep memories of each other for years on end.
The Avatar: The Last Airbender episode "The Cave of Two Lovers" has this in the story of Oma and Shu, who became some of the first Earthbenders, learning from the badgermoles. When he was killed by her tribe, she unleashed rage and vengeance on both until they agreed to work together. An actual in-series example is Sokka and Princess Yue.
Bump in the Night parodied this in the episode "Adventures in Microbia", where Neat Freak Squishington gets unwanted affections from a Germ Girl. Squishy eventually loves Germ Girl back, but ends up having to part ways with her before he and Mr. Bumpy return to normal size.
Danny Phantom has Half-Human Hybrid ghost hero Danny and Valerie, the Ghost Hunter. They date briefly, with Valerie breaking up because of her job, unaware of Danny's ghostly alter ego, but love-lost feelings are mutual during the aftermath... until Season Three.
Parodied in the Drawn Together episode "The Other Cousin" when Captain Hero sees Bleh for the last time before she goes away:
Captain Hero: Maybe it wouldn't work out... I mean, we come from two different worlds. I come from the planet Zebulan and you came from a mom who drank when she was pregnant.
Final Space: Nightfall, an Alternate Self of Quinn, thinks she and Gary are this after she's spent twenty years traveling through hundreds of Alternate Timelines where Gary universally dies, only to find that in the one timeline where Gary lives, he doesn't want her because she's not the Quinn he knows in his timeline. As she puts it:
"Always meant to be together, but never meant to be."
The original series finale of Justice League is called "Starcrossed" and has to do with the fate of the relationship of the Green Lantern and Hawkgirl... though really, it could have been called "Planetcrossed" just as easily.
Miraculous Ladybug: Ladybug and Cat Noir cannot be together or know each other's true identities until after Hawk Moth is defeated, due to the risk of one of them being Akumatized.
Moral Orel has Orel and Christina. They like each other, but their families end up hating each other over different interpretations of the lord's prayer.note Specifically, Trespassers/Trespass vs Debtors/Debts. Christina's family ends up moving away, but Orel later goes out of his way to invite her to his school's dance and later ends up marrying her.
In My Little Pony: Friendship Is Magic, it turns out that Applejack's parents, Bright Macintosh and Buttercup, were this due to Buttercup's real name being Pear Butter. As the two clans were business rivals turned feuding families, Pear Butter and Bright Mac had planned to have a secret wedding a la Romeo and Juliet, but it was broken up by Grand Pear and Granny Smith. Unlike most instances Pear Butter disowned herself from the Pear family staying with Bright Mac eventually giving birth to Big Mac, Applejack and Apple Bloom. It would take years before the families buried the hatchet and by then Bright Mac and Buttercup were dead.
Played with in the Friendship between Gus and Corn Chip Girl in Recess. His father is in the Army. Her father is in the Navy. Do the math.
Parodied by Cartoon Network short Salt 'n Slug (one of their "Cartoons That Never Made It" parody shorts,) about a romance between a slug and a living salt shaker. The salt shaker accidentally kills the slug partway through the intro sequence.
In the 2018 reboot of She-Ra and the Princesses of Power, Hordak and Entrapta collaborate on the interdimensional portal. During their months together, they become close friends with significant romantic tension. However, Catra secretly exiles Entrapta to Beast Island and lies to Hordak about it, telling him that Entrapta returned to the Princess Alliance. Hordak spends season 4 angry and hurt over Entrapta's "betrayal", but he still pines for her. The protagonists eventually rescue Entrapta from Beast Island, shortly before Hordak is taken captive on board Horde Prime's ship, making Hordak and Entrapta literally star-crossed at the end of season 4. Fortunately, they happily reunite at the end of the series.
In the Silly Symphonies cartoon "Music Land", there are two music-themed islands, the uppity Land of Symphony and the carefree Isle of Jazz. The rulers of these two islands, the cello queen of symphony and the saxophone king of jazz, are each disdainful of the other; the king views classical music as highbrow and the queen sees jazz as lowbrow. However, their respective children, the saxophone prince and the violin princess have fallen in love with each other, which leads to the prince being imprisoned by the queen and eventually an all-out war breaking out between the two rival countries. But when their children are both in danger, the feud ends with them all saved and not only their children marrying, but also their respective parents, and a new bridge, the Bridge of Harmony, built to link the two islands together.
Parodied in "Miss Teacher Bangs a Boy", with Ms. Stevenson, who is a teacher, and Ike, who is a young child. Ms. Stevenson genuinely falls in love with Ike, wanting to run away and start a new life with him. She even has sex with him. Of course, since Ike is too young to comprehend all of this, he just kind of rolls with it. In the end, Ms. Stevenson wants to commit suicide with Ike, and tells him to jump off the building when she does. While Ms. Stevenson jumps, Ike, thankfully, doesn’t.
Played straight with Kyle and Rebecca in "Hooked on Monkey Fonics".
Invoked in "Where My Country Gone", The fate of the romance between Butters and his Canadian girlfriend, Charlotte because of a plan made by Eric Cartman in order to smooth things over with the Canadians. The boys even try referencing the story itself, but they fail.
Obi-Wan Kenobi and Satine Kryze in Star Wars: The Clone Wars. He’s a Jedi, she’s the Duchess of Mandalore, it was never going to work out. It takes a dark turn in the episode “The Lawless”, when Satine is killed by Maul. Obi-Wan even admits that he would have left the Jedi order to be with her if she’d have asked him to.
