In the anime and videogame of Xenosaga, the character of MOMO was an Artificial Human reconstruction of her creator's daughter, Sakura.
He went a little further than that with Momo being the 100th Replacement Goldfish he created in a full scale production line of androids with her face. His wife, on the other hand, was none too pleased with seeing a hundred copies of her dead daughter running about the galaxy and mentioned as much.
Something of an unusual example, as MOMO and the others were originally only meant to replace part of Sakura, as she suffered from a disease similar to Locked In Syndrome and MOMO was meant to become a new body for her. It was only after the poor kid bit it that Mizrahi decided to go the whole hog and use MOMO as a full Replacement Goldfish.
This becomes a Crowning Moment of Heartwarming in the third game when Mizrahi tells MOMO that he had long since accepted that he would never get his daughter back, and had truly grown to love his 'second daughter' as a completely separate being.
Scores more heartwarming when Juli herself accepts this fact too.
The Big Bad tried to clone his long-lost love. It ended badly.
Minsc will adopt either Aerie or Nalia (with a preference for the former should they both join the party) as a replacement for Dynaheir, who was murdered by the Big Bad before the game starts.
Actually averted in Dissidia: Final Fantasy, Cid did not create the Warrior of Light to replace Chaos as his surrogate son. He only created him to see if he could create another "perfect Manikin" like Cosmos.
In XCOM: Enemy Unknown, when a soldier that you really like is Killed Off for Real, it is sort of common practise for players to take another soldier, then change their name and give them plastic surgery to create a replica.
Subversion: In Sam and Max: Season 1, Sam and Max actually get a replacement goldfish, and they worry he'll find out.
In Season Two, the Goldfish dies, and returns from Hell to kill them. They replace him in their office with a stone replica naming it as the prophesied leader of the sea chimpanzees.
At the end of Season Three, Max is killed, but Sam meets another Max from an Alternate Universe who had similar adventures, but Sam died in that universe instead. They're each other's replacement goldfish.
The sequel series, Mega Man Star Force, the robot Hollow is a replacement for the Big Bad Vega's dead lover. Ironically, she never pays proper attention to him because he isn't an exact copy, but he ends up developing a soul and falling for her.
In the Nintendo DS game Professor Layton and the Curious Village, Lady Dahlia is a robot, like everyone else in St. Mystere except for Flora. She was created by Baron Reinhold to be a replacement for his dead wife. However, her existence as a replacement for the dead wife was so traumatic to his daughter that he had the robot's memory wiped and the Lady Dahlia personality created instead.
In Final Fantasy VII, Aerith is drawn to Cloud because he reminds her of her former boyfriend, Zack Fair who turns out to have been Cloud's Big Brother Mentor before his death. Aerith's kind and gentle demeanor (though she is quite spunky at times) reminds Cloud of his late mother. Aerith even lampshades the trope in the Gondola Date, then adds that she would like to know Cloud better for the guy he actually is.
Silent Hill example: Maria, who was born from James' wish to be with his dead wife Mary.
In Silent Hill 3, Heather is, in a way, a Replacement Goldfish for Cheryl. Slightly different in the fact that she is the reincarnation of Cheryl and Alessa (who were originally one person to begin with. At the end of the game, she starts going by Cheryl again.
According to the enemy notes and her appearance, in MOTHER 3, Lil' Miss Marshmallow was built by Porky to replace his human maid, Electra, from the previous game (EarthBound), who he apparently had a crush on and who he could no longer be with due to Time Travel problems.
Seems to also be the case with the robotic waitresses in New Pork City that greatly resemble Porky's mother to a tee in both appearance and personality.
This is the backstory behind the Prismriver Sisters from Touhou. A long time ago, a man named Count Prismriver had four daughters, but he tragically died and the sisters were orphaned. Each went their separate ways, but the youngest couldn't bear to part with her sisters, so she created three poltergeists with the appearances and personalities of her sisters.
Reisen Inaba used to be owned by the Watatsuki sisters but after fleeing to earth and becoming an outlaw, the Watatsuki sisters still felt attached to Reisen and named their new pet Reisen as well.
This is also the backstory of Seihou's (Touhou's "sister" series) main character VIVIT; Erich, the developer of Saboten energy, suffered an accident that left him a cyborg and took his daughter's life. Thus, VIVIT was created by him as a replacement for the original Vivit. And because Erich is a bit of a perv, he dressed his robo-surrogate-daughter in a maid outfit.
In Rogue Galaxy, Steve was created as a replacement of sorts for Dr. Pocacchio's son Mark, and apparently has some of Mark's thoughts in his neural network.
This becomes glaringly obvious when you play the prequel to Final Fantasy VII: Crisis Core, when you realise that all of that cool stuff Cloud did? Zack did it first, and Aeris noticed.
In Knights of the Old Republic you have the option to help a woman get back her droid. As it turns out, he became a replacement for the woman's dead husband. In a lot of ways. If you find him, he asks you to end his misery. "Wow. She really misses her droid, doesn't she?"
Super Paper Mario lets you buy Tiptron in place of Tippi/Timpani after you lose her to Count Bleck/Blumiere. You'll want to do so more likely than not.
Mona, the protagonist of A Vampyre Story, is the latest in a protracted line of Replacement Goldfish for the villain, Shrowdy von Keifer. After his mother vanished, he went a little goony (well, moreso than usual - the dialog is peppered with implications that even before the Baroness disappeared, Shrowdy was everything wrong with mama's boys) and started kidnapping young women and keeping them in his castle. It's stated once or twice that Mona's been around the longest of all of them because she bears an uncanny resemblance to the missing Baroness.
In Moon Crystal, Ricky is aided by a mysterious girl named Rosina who claims to be the daughter of Count Crimson. It is later revealed that Rosina is, in fact, an automated corpse; she died long ago and Crimson used the Moon Crystal to bring her back to a half-living state.
Inverted in Tales of the Abyss, where Luke is a replica of Asch, created by the Big Bad prior to the prophesied death of the original in order to die in the original's place. While considered little more than a cheap knock-off by his creator, the people who genuinely care never consider him a replacement, because they weren't in on his creation in the first place and considered the two to be distinctly individual people when they learn the truth.
The one instance this is actually played straight in the game is with Nebilim, who was intended to 'replace' the person she is a replica of on an emotional level.
Actually, Ion is another instance, as the Ion you travel with turns out to be a replica of the original Fon Master Ion, who died two years prior to the game's events. After this Ion is killed as well, he's replaced yet again with another goldfish, Florian.
In Tales of Berseria, Velvet liberates a young Malak from the Exorcists, eventually giving him her deceased younger brother's name of Laphicet due to him reminding her of him. He manages to draw out the soft side of her personality that had buried been beneath her hate and despair some years ago.
Likely unintentional, but in Harvest Moon: Animal Parade, if you decide to start a new game when your child recently grew up, your spouse might suggest to have a second child before your first leaves on their journey (although, you can't continue your file after they leave anyway, sooo...).
Sid Meier’s Alpha Centauri: "I loved my chosen. How then to face the day when she left me? So I took from her body a single cell, perhaps to love her again."
In League of Legends, the scientist Corin builds a clockwork replacement for his daughter, Orianna. Because she had wanted to compete in the league, he also made her a killer robot. She has at least some of the original's memories, but her personality seems a bit limited, and everyone but her questionably sane father finds her unsettling.
Over Blood: It turns out that Milly is a clone from the villain's wife who died, she still has all the memories intact so she would still love him. Didn't work.
In Super Robot Wars Original Generation 2, Lemon Browning is revealed to have been an android (or possibly resurrected cyborg) made by the parents of an alternate universe Excellen Browning, who didn't survive the near-death incident of her backstory. However, her parents quickly realized the disrespect they had done to their daughter, and rejected Lemon (which may explain her name). This is apparently what motivated her to create human-like androids of her own, and why she was actually happy when one of them made friends and betrayed her for their sake.
Way before that, in Super Robot Wars 3, Benkei Kuruma was this for Musashi Tomoe. After Musashi was killed in a Heroic Sacrifice, Professor Saotome called in Benkei to replace him after unveiling the Getter Robo G. Ryouma and Hayato were not please in the least, but the two end up warming up to the pilot, and in Super Robot Wars 4, they go and teach him Musashi's signature attack so that they're at the same level.
Dragon Age II. Partway through the second act, Hawke will meet a "Quentin", who has been killing women throughout Kirkwall to recreate his diseased wife out of their body parts, using Blood Magic.
In the Pokémon fandom, some consider Lyra to be this to Kris, even going as far as to refer to one of the ships involving the former as Replacement Shipping (Ethan x Lyra).
Done subtly, but very creepily in Robotrek on the SNES. Nagisa is an android created by the protagonist's father to look after him. She's also modeled to look like his dead wife, something you can easily miss via dialogue until a flashback midway through the game shows the protagonist's mother.
The Last of Us: At first Joel sees Ellie as a means to an end, and nothing more. As the game progresses, the two bond, and eventually Joel begins to think of Ellie as his surrogate daughter his real daughter Sarah was killed 20 years ago in the game's prologue, and Joel has been trying to bury her memory. He even calls her "baby girl" Like he called Sarah and forcibly ends a firefly attempt to cure the fungus by performing a lethal experiment on Ellie.
Invoked by Bedman in Guilty GearXrd. He kills a Magehound puppy that Ramlethal befriended and then provides her with a replacement puppy. When this new puppy doesn't bite her finger affectionately like the old one did, he explains that the old one is truly gone forever and cannot simply be replaced. Although this is understandably a heart-rending experience for her, this succeeds in teaching Ramlethal about the value of life and leads to her eventual Heel–Face Turn.
Somewhat tragically, from what little we see of Nora before she goes into Vault 111 with her husband and is cryogenically frozen only to be murdered by Kellogg, she has an awful lot in common with Piper. Dark, elegant hairstyle? Check. Solving her problems with a quick wit? Check. Encouraging and coddling a partner who tries to help others and making witty remarks about Jerkasses? Check.
At the end of the game it's revealed that Shaun, the protagonist's son, is actually "Father", the Big Bad of the game. He was released from cryostasis many decades before the player character, brainwashed by the Institute at a young age, and eventually became their leader. Now he is an old man, dying of cancer, and even if the player chooses to side with him and become his successor, they have no more than a few months together. However, he had a synth version of himself as a child made, which he leaves to the protagonist as a gift. The synth does not seem to be aware of what he is and genuinely believes himself to be the protagonist's son, and if you choose to adopt him, the player will respond in kind.
Inverted in Brütal Legend, when TitansAscended to a Higher Plane of Existence, their servants, the Tainted Coil, tried to create new masters for themselves to serve. However, like everything they made, their creation, known as Humans, became only a pale copy of what their masters could accomplish. The knowledge that their beloved masters were well and truly gone drove them insane with rage and grief, that they vented on their creation.