The sheer brutality of the main plot twist in Frozen did this to the Hans/Anna ship, and by extension, every other Hans-related ship. Essentially, Hans reveals he only ever cared about getting the throne, and Anna was the easier sister to seduce. He then explains how now that she's dying, all he needs to do is kill Elsa to end the winter and become a Villain with Good Publicity. Said Evil Gloating is done with a smug, satisfied smile. Word of God confirms that the character in question is and always was a sociopath.
Reinforced in Frozen II, when the protagonists are playing charades and Anna's attempt to mime "villain" prompts her to identify "Hans" as a clue, with Elsa identifying Hans as "Irredeemable Monster".
The Twilight Sparkle×Flash Sentry ship sunk in Legend of Everfree. Flash transfers his affections to the human Twilight Sparkle who's creeped out by this and gets a different love interest soon after. Sunset Shimmer confronts Flash over how unhealthy this is and convinces him to move on from Princess Twilight, as their living in another dimension and being busy such she no longer visits means a relation is unlikely to work out. Flash has since had Ship Tease with Sunset.
While Spike×Rarity gets tease in the parent series, Word of God has stated that Spike being a dog in this world precludes anything romantic with human Rarity.
Live Action
For people who haven't read the books, the scene in Jurassic Park III between Ellie's kid and Alan was a major blow when we discover he is not the father. Fortunately, Jurassic World Dominion rekindles their romance.
Star Wars did this to a certain extent with Luke and Leia (partly because George Lucas had yet to make several crucial writing decisions when he created A New Hope). The first film left the possibility that Leia would end up with either Luke or Han open. In the second movie, it became obvious that Leia and Han were the central romance, despite the ever-infamous and literal Kissing Siblings scene. (In-between the two films, Lucas plotted out a possible second film that also included shipping between Luke and Leia; it was later adapted as the novel Splinter of the Mind's Eye; other spin-off media, such as comics, carried on assuming that Luke and Leia were the OTP). In the third movie Lucas sprung the family relation card on Luke and Leia, revealing them to be secret twins! It's safe to say this sunk Luke/Leia permanently (while adding Squick elements to the first two films as a result).
The Force Awakens gets a subversion. Han left Leia after their son, Ben "Kylo Ren", went to the Dark Side. Han reunites with her briefly, but by the end of the film is murdered by Kylo Ren. It appears as though Han/Leia is done for good, but the two were still very much in love while separated, so it could be debated whether or not this was an actual ship "sinking".
Finn/Rey developed a small but devoted fanbase after the release of The Force Awakens, with fans interested in seeing an interracial couple depicted in a franchise as big as Star Wars; the character's final scene together in which Rey speaks tenderly to an unconscious Finn about seeing him again and kissing him on the forehead didn't help. Despite the actors stating more than once that Finn and Rey were only friends, the fans persisted; it wasn't until John Boyega's Cannes 2016 interview that the ship was finally sunk. Boyega clarified once more that Finn and Rey are just friends who did not share romantic interests and ended with a statement that the romance in the next installment would not go in the direction some fans might suspect, prefacing with another reminder that Rey and Finn are only friends. The Last Jedi lives up to this, with Finn and Rey being separated for almost all the film and getting Ship Tease with Rose and Kylo, respectively.
Finn/Poe shippers got a crushing blow when, in an interview given after Star Wars Celebration, Boyega confirmed Stormpilot won't become canon either. See above.
Reylo (Rey/Kylo Ren) in The Last Jedi when they can't reach an agreement on what to do after tag-teaming to kill Snoke: Kylo wants them to rule the galaxy together, she wants them to destroy the First Order and join the Resistance together. They briefly engage in a fight before going their separate ways, committing to opposite sides in the war. Rey sparing him and his conflicted gaze on her at the end suggests they still care, but they certainly aren't getting together anytime soon. Later, despite sharing a kiss, the ship sinks for good when Kylo finally dies.
If you liked the weird romance between Stu and Jade in the first Hangover film, the sequel will disappoint you.
Hawkeye/Black Widow was a major ship ever since The Avengers. It was completely and utterly sunk in Avengers: Age of Ultron, partly due to the developing Widow/Banner relationship, but mostly due to the reveal that Hawkeye has a wife and two kids, with a third on the way. They remain Like Brother and Sister, however, and the rest of Hawkeye's family loves her just as much. The kids refer to Widow as "Auntie Nat," and the third was named after her. Heck, any major ships involving Banner, Hawkeye or Black Widow were completely and utterly sunk in the span of about two hours. Examples include Banner/Betty (the latter of whom hasn't appeared in an MCU film since 2008's The Incredible Hulk), Hawkeye/Mockingbird (Mockingbird was instead relegated to a supporting character in Agents of S.H.I.E.L.D., with Lance Hunter replacing Clint as her love interest), and Black Widow/Captain America (who are completely platonic).
In another twist, Avengers: Infinity War sinks Banner/Black Widow with their only on screen moment being a awkward hello and signs they’ve both gotten over each other since Ultron, with no attempt to further their relationship. Anthony Russo weighed in saying, "Look, he disappeared for two years. She's pretty self-sufficient, she didn't wait around for him. There's sort of unspoken truth that there's need to be a spoken resolution". Some fans weren’t fussed about the ship sinking, feeling the Banner/Black Widow relationship felt very forced in retrospect to them on Joss Whedon’s part.
Despite two movies that featured their relationship as a central plot point, Thor/Jane Foster was sunk in Thor: Ragnarok, with the God of Thunder mentioning offhandedly that there was “mutual dumping" between that film and Thor: The Dark World. The Out-of-Universe explanation for this is that Natalie Portman had no interest in returning as Jane after Patty Jenkins, who was originally attached to direct The Dark World (whom Portman personally vouched for), departed the project over creative differences. Since Jane was already seen as The Scrappy to a lot of fans, this wasn’t a major cause of upset, and thus Thor moved on with a new implied love interest in Valkyrie, while Kevin Feige confirmed his other ship teaseLady Sif is still out there somewhere. Eventually Jane returns in Thor: Love and Thunder and while it seems that their romance can be reignited again, said hopes ended up dashed when Jane succumbs to terminal cancer and eventually dies at the end of the movie, leaving Thor single once again.
Poor Peter and Liz in Spider-Man: Homecoming as their potential relationship is sunk when it’s revealed Liz’s father is The Vulture and Peter has to leave Liz at the prom to stop him as Spider-Man. While bittersweet it’s fitting as Peter and Liz also failed to hook up in the comics and really a lot of high school romances don’t work out. Spidey has moved on in Spider-Man: Far From Home with a new interest in Michelle, much to the disappointment of Spider-Man/Shuri shippers but come Spider-Man: No Way Home, even the latter ship ended up being sunk when Peter at the end of the movie, is forced to erase everyone's memories of his existence before the multiverse could collapse and while it seems that Peter tries to make them remember at her request, in the end he ultimately decides to leave her in the dark to keep her safe from enemies who are willing to harm her due to her association with Spider Man.
There's also Aunt May's comment about not liking Tony Stark, which negates their brief ship tease from Captain America: Civil War and Pepper returns in the ending anyway. In Spider-Man: Far From Home May dates Tony's bodyguard, Happy Hogan but it’s left ambiguous and doubtful whether it’s an actual serious relationship between them.
The Russo Brothers sent another Shipping Torpedo to Cap and Sharon Carter aka Agent 13 in Avengers: Endgame as through Time Travel Cap returns to his old flame Peggy Carter in the Golden Ending. Since fans were fairy Squick-ed out at Cap kissing his former’s love niece, there were no real complaints though it makes you wonder why Cap/Sharon needed to be a thing in the first place.
Endgame also proved to be the final, decisive nail in the coffin for Romanogers fans, due to the ending mentioned for Captain America above as well as Black Widow’s unalterable death on Vormir.
In The Hunger Games: Mockingjay Part 1, Katniss confirms out loud that she's in love with Peeta, thus sinking the Galeniss ship. And if that didn't sink it, then the revelation in The Hunger Games: Mockingjay Part 2 that Gale may have had a hand in creating bombs that killed several innocent citizens, including Katniss's little sister definitely did.
In Space Jam: A New Legacy, is revealed that Bugs and Lola separated off-screen. And while a breakup isn't usually enough to sink a ship, the film makes it clear that their relationship is completely platonic, eliminating the possibility of them getting back together.
that Spike being a dog in this world precludes anything romantic with human Rarity.