In one of the Cristina Memories of Assassin's Creed: Brotherhood, Ezio threatens to hunt down and kill Manfredo (Cristina's fiancé) if he ever does anything to hurt her. (Cristina had been Ezio's girlfriend 2 years prior)
At the end of Azure Striker Gunvolt 2, Joule loses her memories of Gunvolt after she returns to her original being, Mytyl. Seeing Mytyl living the life of freedom and normalcy (which is what Gunvolt wanted for her in the first place), he doesn't have the heart to take her away from it.
In Chrono Cross, Perky Female Minion Harle ends up developing actual feelings for Serge during her travels with him in Lynx's body. When she realizes that her feelings cannot prevent her from completing her true mission (obtaining the Frozen Flame for the six Dragons), there's a scene where she breaks down crying and leaves the party. Later, after Serge's group successfully enters Chronopolis and defeats Lynx and FATE, Kid attempts to destroy the Frozen Flame. Harle suddenly reappears and begs Kid not to do it, as doing so could also harm Serge. She manages one last sad goodbye to Serge before disappearing to join the other Dragons and form the Dragon God.
Cry of Fear has the protagonist Simon who is in love with a friend of his named Sophie, but she admits to him that she doesn't feel the same way, with her apparent suicide being symbolic of Simon realizing he never had a chance. In the Golden Ending, he comes to terms with this and is genuinely happy that she still visits him and her new boyfriend treats her well.
In Cursed by Jet Dogs Studios, you eventually discover that your husband from a long distant past life loved you enough to sell his soul to get you back. When confronted by the demon with whom both he and your current fiancé have signed a pact for your sake, you are suddenly interrupted as your long-past husband attacks the demon while yelling at you to run and undo his mistake.
If the PC takes up with Anders after Fenris breaks it off, the latter says simply to the former: "Be good to him/her. Break his/her heart and I will kill you." Considering that Fenris and Anders hate each other with the burning of a million suns, and that he's still very much in love with the PC, this is especially touching.
A very similar thing happens if the PC initially goes for Isabela and then switches over to Merrill, but this is far less surprising since Merrill's cheerful, Cloudcuckoolander, and somewhat naive personality tends to cause the rest of the party to have a Big Brother Instinct toward her.
Dragon Quest V: Bianca assists the main character with the Engagement Challenge despite her own feelings for him, and would have left them completely unvoiced if Nera hadn't figured it out and spoken up on her behalf.
In Final Fantasy VI, Locke's beloved Rachel returns to life just long enough to release him and tell him to be happy with his new love, Celes.
Final Fantasy VII Remake has a Relationship Values system between Cloud and the two female leads. If the player pursues Aerith, she warns Cloud in a dream against falling in love with her; it is implied throughout the game that her connection to the planet means she is aware of how the story is "supposed" to go and her fated death at the hands of Sephiroth later on. Given by Cloud's expression as she says this, it's already too late.
It's more out of guilt than anything — Camus decides to leave Nyna be, probably feeling too guilty about what happened to Hardin, her husband...thing is, Hardin died during the events of Mystery of the Emblem, and Nyna has nowhere to go. Instead of appeasing her, he has this in mind and vanishes, presumably returning to Valentianote The setting for Fire Emblem Gaiden, where he wound up after the first game and be with Tatiana, a priestess he himself fell in love with. This actually backfires, as Nyna is so fed up with the utter shit that her life has been that she decides to pursue him and try having control of her own life, leaving Archanea in Marth's hands.
In Blazing Blade, should Priscilla reach maximum support/fall in love with either Heath or Guy, both of them choose to leave her in their respective paired endings, as she's a noblewoman and they are a traitorous mercenary and a swordsman from the Sacae Plains, respectively. They have this in mind when leaving her, but she winds up sad anyway. However, if Priscilla's love interest is Erk instead, then this gets subverted as Erk's connections to the Count and Countess of Reglay gets him the peerage to marry Priscilla.
Cordelia in Fire Emblem: Awakening seems to want this at first for Chrom, as she feels unworthy to be with him. Bad thing, some of her quotes in-game related to Chrom are not re-written to reflect this... Played for Laughs after Chapter 13, if Chrom's wife is Olivia. She sees him hugging a beautiful girl and believes they're in cahoots, prompting her to step in and tearfully declare she will not stand between him and his Second Love. Things is... the girl is Chrom's Kid from the Future Lucina, so she's saying this to her own daughter. Once Chrom explains what's going on, Lucina and Olivia share a hug.
Hubert in Fire Emblem: Three Houses is very much in love with Edelgard and has been since he was a child, to the point he would gladly give his life for her or go behind her back to do something for her sake. At the same time, he makes it apparent that it doesn't matter to him if she reciprocates those feelings or simply views him as her close confidant and friend. In fact, on the Crimson Flower route he's willing to try and set upByleth (either gender) with Edelgard both because they can serve as a better emotional anchor for her and he knows she does have strong romantic feelings for them.
The second game, Moonlit Lovers, has Ranpha briefly going through this. Due to a series of misunderstandings, she assumes that Chitose, the newest member of the Moon Angel Wing, is poor and tries to pair her with Tact, thinking that she needed him more (due to watching a movie where the heroine did a similar thing). After this is cleared up, she confesses to Tact that she's worried about being too demanding in their relationship, until he proves he's willing to put up with it if that's what it takes to be with her.
The manga based on the videogame has Ranpha willingly stepping aside once she understands that Tact loves Milfie, both for his sake and for Ranpha's own friendship with Milfie.
In Kingdom Hearts, Riku lets Sora and Kairi be together through four words: "Take care of her." Made funny at the end of his story mode in Kingdom Hearts: Chain of Memories when he discovers Sora sleeping in a pod to regain his memories and he comments "I told him to take care of Kairi, and here he is taking a nap!"
King's Quest IV: Despite being head over heels infatuated with Rosella, and with his kidnapper promising the Standard Hero Reward of marrying them, Edgar says it with a single red rose under the door of her prison - the key's attached. It works out for them in the end.
I Was a Teenage Exocolonist: If Sol tells Cal to back off from his crush Tammy, Cal cries but begrudgingly lets them go with her, on the condition that Sol takes good care of her.
In The Legend of Heroes: Trails into Reverie, if players pick a Love Interest in Rean's first chapter of the game, then at the end of the game, Jusis apologizes to a different version of Rean, whose combined form with the Big Bad of the last game ended up being the Big Bad of this game, because he doesn't bring Rean's chosen Love Interest with them while rescuing Rufus from his Zero-Approval Gambit. This version of Rean responds with this trope, claiming that as long as they're living in a brighter future, then that's enough for him.
Played with with Groose in The Legend of Zelda: Skyward Sword. At first, Groose harboured a deep resentment for Link due to his close relationship with Zelda, and didn't even want to allow the pair some time alone for the Goddess Ceremony. But as the game goes on, he grows to see Link as a friend and that resentment all but disappears. When Link returns to the Sealed Temple to wake a long-time sealed Zelda from her stasis, Groose tells him Zelda is waiting for him and doesn't even try to follow. He seems to have completely come to peace with his Hopeless Suitor status, and merely wants to see his new friend and his crush happy.
Paya, Impa's granddaughter, has a massive crush on Link. However, she writes in her diary that, although she feels a pain in her chest at the thought, she believes Link and Princess Zelda would make a nice match. She also promises to support them if it were to happen, and writes that she was simply grateful to Link for allowing her to experience love, whether or not he returned it.
An unnamed castle poet was in love with Princess Zelda 100 years ago. It's implied that he may have even attempted to confess to her, but was rejected because she already harboured feelings for her appointed knight, Link. At first, he resented the knight, because he believed the Princess of Hyrule belonged with someone of royal or noble lineage instead. However, when the Calamity struck, he witnessed Link sacrificing himself to protect Zelda, and Zelda's love for him awakening her dormant powers. The act inspired him to dedicate his life to write a song specifically to help the knight once he was resurrected, and before he died, he entrusted both the song and its purpose to his student: Kass, who knew exactly who Link was all along despite not showing it, and each of the riddles he had Link solve all over Hyrule were in fact different parts of the whole song.
Hyrule Warriors: Lana is revealed near the end of the first act of the game to be Cia'sgood sidemade manifest, and thus shares Cia's feelings for Link, though in a far less yandere way. After the final fight with her, a dying Cia asks Lana how she can go on knowing that Link will never choose one of them, Lana tells her that you don't always get the person you think you deserve, and she can accept that.
Even though Goro Majima in Yakuza 0 has feelings for Makoto Makimura, after everything she'd been through as a Living MacGuffin being passed around by various yakuza factions, he realized that she'd be better off living a normal life without him and cuts all ties with her at the end of the game, leaving Makoto with no idea who her mysterious protector was. Fortunately, though she does go on to get married and have a family, she does eventually find out who her savior was in Yakuza Kiwami 2. This comes back in one of Majima's karaoke songs in Yakuza Kiwami 2, as well. The song is called "Shiawase Nara Ii Ya" (As Long As You Are Happy), and plays over a montage of Makoto and Majima. However, the real Tear Jerker is in the vocals. In the beginning, Majima sings in a screechy, off-beat, over-the-top Majima voice, but the further he gets into the song, the more his natural beautiful singing voice comes through, and in the end, he is singing completely in earnest, his voice brimming with grief, longing and regret.
There is also Majima's relationship with Taiga Saejima. Majima spends obsessive amounts of time ensuring that Saejima will have something to come out of prison to, in spite of being quite sure that Saejima blames him for going to prison in the first place, and intends to kill him the second he gets out.
Tomizawa in Like a Dragon: Infinite Wealth ends up feeling this way towards his ex-wife, who divorced him while he was in jail for a crime he didn't commit. When he learns that she has since moved on to somebody new and the two of them have plans to leave the country, he figures it is best to just let her go someplace she can truly be happy instead of trying to worm his way back into her life. At least the two of them get to have one last conversation before she leaves, even if it's off-screen.
Love & Pies: When Sam tells Amelia that Joe once dated Edwina, Amelia get worried that Joe might cheat on her for Edwina like what her ex-husband did to her. When Amelia tells Edwina about her relationship worries, Edwina, who's just slowly warming up to her, advises her that she should let go of her past because Joe is truly the one for her and Edwina trusts him that he won't cheat on Amelia. While it's true that Joe dated Edwina, it was long before Amelia returned to Appleton, and it was just a short fling.
In Lufia II: Rise of the Sinistrals, Tia tries to talk Maxim out of being a warrior, because she cannot endure the thought of something happening to him in battle. She decides to give him up when she realizes that this is a part of Maxim which makes him happy, surrendering him both to his passion for battle and his future wife Selan.
Shepard:Tali, if you're scared, I don't blame you. But I don't want anyone else, [takes her hands] I want you. And I'll do whatever I have to to make this work. Tali:[nervously] I...I...I wouldn't blame you if, but... [quietly] Oh, thank you. You don't know what that... thank you.
If you romanced Liara in the first game, in the DLC Lair of the Shadow Broker, she will tell Shepard that she does not want to burden him/her and that if s/he wants to move on, she won't hold it against him/her. It's a part of Liara's character. She'll say the exact same thing when she thinks Ashley or Kaidan is in love with you, though her subsequent bout of Poor Communication Kills calls into question how truthful she was being.
Shepard actually attempts this with Tali in the continuation of their relationship. There's no romantic rival or anything, but Shepard accepts that Tali must leave him (at least until the war is over) to stay on the planet that they just won for her people, as said planet has an almost religious significance in her culture, and she's wanted to live there all her life. Tali has other plans.
Shepard: You going to be okay? I know working with the geth will be difficult- Tali: I'm not staying. I'm coming with you. [pause] Shepard: I wasn't going to ask... Tali: Why not? Shepard: Because I respect you, dammit! You think I don't want you to come with me? Tali: So ask me. Shepard: Tali... Tali: I don't know how much time we have left. I don't know if we can beat the Reapers. But whatever happens, I want to be with you. Shepard:[smirks] I bet you say that to every guy who gets you a homeworld. Tali: [looks directly at him] Only the cute ones. Shepard: You know I'd understand if you needed to stay? Tali: I know. [...] Tali:[while watching the sunset] It is beautiful though. Isn't it? Shepard:[looking directly at Tali] Yeah... it is.
If you romanced Liara in 1 and Tali in 2, then commit to Tali and take Liara on the Geth Dreadnought, after a few moments where it appears touch-and-go, Liara tells Tali that she simply hopes the two of them are happy together.
Snake's jealousy of Naomi for her relationship with his best friend is quite clear in Metal Gear Solid 4: Guns of the Patriots, but at the same time he becomes furious with her when she breaks his heart.
In Persona 3Portable, if you're playing as a girl you have the option to start a romantic relationship with Shinjiro Aragaki. He knows he's going to die soon in one of 3 different ways, so even though he loves the protagonist, he knows that starting a relationship would cause her nothing but pain, so he does his best to deter her for her own sake. With enough persistance you can get him to overcome this (ending in an implied Optional Sexual Encounter), but even when you talk to him after that he still tries to keep telling you that you're better off with somebody else.
In Persona 5Royal, this is the feeling of Takuto Maruki for his girlfriend Rumi. Her parents were murdered during a break in of their home and Rumi was left in a state of catatonic depression as a result of witnessing the event, with the mere mention of her family being enough to cause her to have full on mental breakdowns. Desperate to help her and seeing that she's unlikely to recover through normal means, Maruki's persona, Adam Kadmon, awakens and heals her shattered mind by erasing all her memories of the event... as well as her memories of Maruki. While this greatly saddened him, he chose to distance himself for her own sake so that she could live her own life and without the possibility of him doing anything that might cause her to relapse. However, this ended up being the catalyst for Maruki becoming the embodiment of man's despair.
In Pokémon Ultra Sun and Ultra Moon, Lusamine is reunited with her missing husband Mohn but realizes that he's lost his memories of her and his family. Seeing that he's happy how he is, she allows him to go on his way while finally obtaining closure herself. (The reunion was much happier in the anime, where he regained his memories.)
Portal 2: Implied to be the reason GLaDOS sends Chell away at the end; hints in the tone and contents of the ending songs indicate she lied about deleting Caroline to drive Chell out of the Aperture Science Testing Facility because she knew the machine would drive her into an amoral testing frenzy again, and wanted Chell out of her reach before she lost control.
Quantum Protocol: In Leo's side story, his friend, Luke, is a Hopeless Suitor for Aurora/Alyssa. He ends up distraught when he realizes Aurora has a crush on Leo. After Luke gets over his depression from failing to flirt with Aurora, he decides to help Aurora and Leo get together.
If you complete a True Pacifist run on Undertale, and then reboot the game, you get a little surprise: Flowey appears, and begs you not to reset. He says that everyone is finally happy and got a perfect ending, and that only the player could ruin it now. He then asks of you, "Let them go. Let Frisk be happy." Believe it or not, a large amount of players had admitted to deciding to never reset and play the game again, unable to bring themselves to do it after that message. That's right, the game itself asks you to do this for the characters.
One of the three endings to The Witcher 3: Wild Hunt gives a rare non-romantic example, when Geralt and Ciri part ways so she can become the Empress of Nilfgaard, which is best summed up by one of the finishing lines.
Geralt: Traveled half the world to find you, but I never intended to force anything on you.
In Xenoblade Chronicles 1 it is obvious that Melia has a crush on Shulk. However, he is completely oblivious, and shortly after that, Fiora is revealed to be alive, but under the villain's control. Shulk does everything he can to get her back, and once Fiora joins the team, Melia is happy for them and confides to Sharla in an end game heart-to-heart that she has decided to give up on trying to win Shulk's heart and let him be happy with Fiora.
, you eventually discover that your husband from a long distant past life loved you enough to sell his soul to get you back. When confronted by the demon with whom both he and your current fiancé have signed a pact for your sake, you are suddenly interrupted as your long-past husband attacks the demon while yelling at you to run and undo his mistake.