All three of Fate/stay night's key human characters have parent issues. Shirou is an orphan, and the man who adopted him is also dead. Rin is living alone, her father having died in the previous Grail War; the man who's been her guardian since then is in fact the Big Bad, and her father's killer. Worst off by far is Sakura: her parents gave her to a foster family years ago, and she's been suffering horrific abuse at their hands ever since.
Inverted in the prequel, Fate/Zero — Kiritsugu (Shirou's adoptive father, and protagonist) left Ilya, his daughter, knowing that he can't be reunited with her, which is the reason for her strange relationship with Shirou in Fate/stay night. Incidentally, Kiritsugu himself killed his own father, Noritaka, after his experiments led to the death of Shirley, Kiritsugu's friend and Noritaka's assistant, along with the slaughter of the village they'd been living in. He later shot down a plane with his mother-figure on it to prevent a zombie outbreak.
It's also applicable to Tsukihime. Shiki's biological parents are dead. His foster father died before the start of the story and is the plot catalyst. Only passing mention of the mother, it's assumed she died. Arihiko has no family left except his sister. Ciel's parents are dead because she killed them. Hisui and Kohaku don't even know their surnames let alone their parents. Most of the rest of the cast aren't people who actually would have families of any sort. An exception is made for Satsuki, who apparently has a healthy home life. Maybe that's why her route was removed?
The parents of Kotomi in CLANNAD don't seem to be very present in her life despite being famous scholars. We later find out why when it's revealed that they died in a plane crash. And they loved her. A lot. Until the very end. But Kotomi herself was so traumatised by their deaths that she convinced herself they were in permanent travels and dedicated herself only to her studies. There is also Tomoya, who is estranged from his father; given the fact that said father was responsible for injuring his arm in a drunken fit and thus preventing Tomoya from ever fulfilling his dream of becoming a basketball player, it is not surprising that it should be so. At one point Tomoya even leaves home to live with Nagisa and her family because of issues with his father; however, it is hinted that they are on their way to healthier relationship in the last episode of the anime, and in fact Tomoya's dad did try to raise him well at first but succumbed to depression at some point and became an alcoholic..
The trope is subverted with Nagisa's parents, who shower her and each other with affection, but then again, they did not pay much attention to her when she was a child due to their work and because of that Nagisa nearly died; one could say that it is a rare case of the trope evolving into a normal family situation.
Tomoya's relationship with Ushio. Not only does Tomoya end up mirroring the relationship with his own father, but by becoming a doting parent when Ushio is 5 years old, mirrors the relationship with Nagisa and her parents.
Ryo Sasaki from Crescendo ~Eien Dato Omotte Ita Ano Koro~ stands out — not only did his biological parents put him up for adoption when he was little, his adoptive parents died in a car accident a few years before the events of the game. He's been living with his older stepsister ever since.
The Ace Attorney series adores this trope, especially when it can be used for a murder case. Phoenix Wright himself is one of the few main characters who doesn't seem to suffer from this, as his parents are never mentioned at all.
Edgeworth's father was killed by Manfred von Karma 15 years ago (leaving Edgeworth with the vision that he himself could have been the culprit), which the fourth case of the first game is centered around, and since Miles was adopted by von Karma it can be assumed his mother is dead as well.
Mia and Maya's father are never mentioned, though the latter is implied to have left them due to Kurain Village's female-centered way of life. The Fey sisters' mother went missing during the events that are the background of the first game, though she reappears as Elise Deauxnim and is killed in the third game.
Pearl Fey's father left the village for similar reasons, and then Pearl's mother gets arrested for assisting in a murder so she's out both parents. Morgan Fey's first husband also left the village, taking Dahlia and Iris with him. Later, he abandoned Iris at the mountain temple,
Apollo Justice's family is completely unknown. In the fourth case, Thalassa Gramarye is revealed to be his mother, and he is actually Trucy's half-brother as she is Thalassa and her second husband's child. It is also revealed that Apollo's father died in a stage accident a year after Apollo's birth, which led to Thalassa abandoning him.Dual Destinies also implies that no one ever adopted Apollo after he was orphaned. The scene that suggests this is when Apollo is trying to comfort his best friend, whose mother had recently died.
Trucy never knew her mother, and her father, Zak Gramarye, abandoned her at age 8 to save himself from a guilty verdict. She never sees him again (as the only time he resurfaces following his disappearance saw him be murdered the very same night), while Phoenix takes her in as his adoptive daughter. She never knew her mother because Thalassa Gramarye was injured in a rehearsal, that left her blind and with amnesia.
In Investigations this happens two cases in a row. Lauren Paups never knew her father since he was arrested for murder when she was very young and then came to work at the same house as her under a false name. She never found out who he was until (once again) after his murder. The following case focuses on the hunt for the murderer of Kay Faraday's father, seven years before the rest of the game.. Kay's mother is never mentioned, so it can be assumed she's either dead or not living with Kay's father. After her father's murder, Kay lives with her mother's relatives.
Ema and Lana Skye's parents died in a car crash when Ema was little, resulting in Lana's Promotion to Parent.
Athena Cykes's mother was murdered when she was a child and she witnessed it first hand, with enough involvement to make her a prime suspect. We don't even know anything about her father.
And all this doesn't even account for all the more minor characters in the games who suffer from this trope, such as Sean and Ken Dingling and Machi Tobaye.
Happens all over the place in Gyakuten Kenji 2/Ace Attorney Investigations 2, a lot of which is relevant to the story.
The fathers of Horace Knightley and Simon Keyes are, respectively, Issac Dover and Dane Gustavia, the former of which is the murder victim to the latter and Gustavia himself abandoned Keyes after he failed to appear to help him win a dessert contest as a boy.
Katherine Hall is the adoptive daughter of Jeff Master, who himself is in prison on false charges stemming from the IS-7 Incident. She doesn't know who her real parents are.
Sebastian Debeste's mother is heavily implied to have been made to "disappear" by the hand of his father, Blaise.
John Marsh's mother is the cousin of Justine Courtney and he is the illegitimate son of the real president of Zheng Fa, Di-Jun Huang. His mother died when he was younger, which is why he went to live with Justine, and his father was murdered by Sirhan Dogen on the orders of Blaise Debeste, Patricia Roland, and his body double the very night he went to visit his son for the first time while he was still an infant.
Emi lost her father in the same car accident in which she lost her legs.
Hanako's parents died in the house fire in which she received her scars.
Lilly's parents moved to Scotland, leaving her older sister Akira to take care of her.
In Hatoful Boyfriend, the player character lives by herself in a cave. In the full version, she starts looking for employment to support herself. In "Bad Boys Love", it's confirmed that she's an orphan; her parents were killed trying to mediate a hostage situation.
Ryouta lives with his mother, who is elderly and too unwell to look after him. He, too, works to support both her and himself, and the climax event of his route is her death, leaving him completely alone. In "Bad Boys Love", it's mentioned that Ryouta's father died of a jungle fever when he was very young and his final request triggered the plot.
Yuuya was forcibly evicted from his family when his mother remarried Mr. Le Bel. "Bad Boys Love" reveals that he crushed the egg Le Bel fathered to replace it with his brother Sakuya, to ensure the latter would survive - he was supposed to throw away Sakuya's egg.
In "Bad Boys Love", Kazuaki and Nageki are revealed to have grown up in an orphanage and considered each other brothers despite being different species.
In Nekopara, Chocolat and Vanilla were found on the side of the road by Kashou and his sister when they were very young.
Riki, the protagonist of Little Busters!, has been an orphan since he was only a child. This is relevant to the plot in three ways: firstly, he became such great friends with the Little Busters in the first place when Kyousuke was able to drag him out of his depression, secondly, because the only family he's shown to have is a guardian he clearly doesn't hold any real fondness for meaning he's even more dependent on Kyousuke and the other Little Busters than he otherwise would be, and thirdly, because Refrain shows that it was witnessing his parents' death that made Riki closed off from and scared of the world, unable to go out there himself on his own.