In Route148 now elderly Frank tries to make sense of the situation in which he was taken in by the Reed family. Also his grandson Linton, one of the comic's main protagonists, is noticeably lacking in the parental department.
In El Goonish Shive, two main characters have divorced parents, one is technically an orphan and one hates her overbearing, borderline-oppressive Education Mama so much we might as well throw her in too. Two have had their fathers show up, though not on-screen (one in a one-sided phone conversation, the other from outside a room). Oh, and of the remaining main characters, one is an Opposite-Sex Clone of the other, and was hence adopted by the same Open Minded Parents, who seem a quite a bit less concerned about the weirdness going on than they should be.
Antimony Carver from Gunnerkrigg Court: Her mother, Surma, dies just before the start of the story from an unspecified ailment that had hospitalized her since about the time of Annie's birth. It turns out that her life force was being drained into Annie as Annie grew up. And Annie's father, Anthony, is one of the most mysterious characters in the comic. Only seen in flashbacks and greatly obscured, he disappeared soon after his daughter started at the Court. He's easily the biggest speculation-bait in a series filled with Epileptic Trees, his current situation, personality and feelings towards his daughter as mysterious as when the comic started.
In Fans!, when it is learned that Alisin has an unknown blood disease which appears to be slowly killing her, the Worthingtons decide to give her whatever she wished for, including, when she rebelled against their over-protection, her freedom. While it seems that they continued to give her any money she asked for and poured vast sums of money into finding a cure, they otherwise had no part in her life afterwards. This is entirely in Alisin's Back Story; the only appearance which Senator Worthington makes at the time of the main story is on television, and Mrs. Worthington is seen only in flashbacks.
Five-year-old prodigy Gin in Jackie's Fridge is for all intents and purposes being raised by Melissa and Ada. Generally played for laughs, this takes a mildly tragic turn: when she gets injured on the playground and has to go to the hospital for stitches, her parents' only reaction is that Melissa interrupted their game of disc golf. It's also then that Melissa learns that they had never given her any gifts — ever.
Gordito from The Adventures of Dr. McNinja was raised by his single father after his mother's death. After his father's death, he was raised by his paleontologist uncle. Now, he's the Robin to Dr. McNinja's Batman.
The title character of "Little Dee" has become lost or separated from her parents. The forest animals who stand in for her family make periodic (and increasingly more half-hearted) attempts to find them.
In the first "season" of The Wotch, the families of the characters are quite absent. The second starts bringing them into scenes, though.
Mostly subverted in Dominic Deegan. The title character's family is pretty solid; the only estranged child is Jacob, the oldest of the three, and that's because he used the youngest, Gregory, as part of a necromantic experiment which almost killed Greg and got him thrown out. Mr. and Mrs. Deegan are in their sixties and still very much in love with one another. The only borderline case is the Travoria family. They started out as a whole family, but Mr. Travoria was killed by Mrs. Travoria, Mrs. Travoria was killed by a royal knight she picked a fight with (as she tried to drive Luna to suicide), and the oldest sister, Amelia, was killed by a thief who tried to use his friend/partner as a pawn in a scheme to kill her husband and claim his vast riches.
In The Order of the Stick, Roy's father died of old age a few years before the story starts, and it seems that his mother must have died at some point since he meets her in the afterlife. Haley's father is a famous thief who is currently imprisoned in a faraway country, and her mother died when Haley was very young. Elan's mother was a Chaotic Good barmaid who divorced from her husband, a Lawful Evil Overlord, over alignment difference, and she raised Elan while he raised his twin brother Nale. Durkon's parents are unknown, although he seems to have had an uncle who he visited periodically; however, Durkon was banished from the dwarven lands and hasn't seen his uncle since. Vaarsuvius' parents are unknown, and when V hit puberty, V was adopted by a wizard who taught V magic, and then threw V out some time later to see the world. Belkar's parents are unknown, though there IS an aunt mentioned who may be as evil as Belkar.
Recloak's entire family but for one of his younger siblings were killed in front of him. As for Xykon, well, he is a Self-Made Orphan.
Elan's father has been recently introduced; on meeting his father for the first time, Elan comments: "Growing up without a father was totally worth it just for that reveal. "
Megatokyo's Miho has no known relatives, and — in fact — lives in the back room of a dance club. Theories as to why this is range from: they died from whatever mysterious disease she currently suffers from to she ate them. Fred Gallagher has been less then helpful.
Most of the main characters in Errant Story suffer from Parental Abandonment. Jon and Sara's father was killed by assassins before their mother died of an illness, Meji's Elven father had a fling with her mother on a diplomatic visit and later tried to have her killed upon learning he had fathered a Half-Elf, and Ian's mother was apathetic and neglectful towards her children until she killed herself and Evelyn in a fire.
Another The Wotch-related example is Alex King from Cheer!. Her wealthy parents are still alive, they just don't seem to care. Early on it's revealed that she even receives her allowance by direct deposit, and a Christmas comic depicting the cheerleaders with their families shows her strumming her guitar by herself.
In No Rest for the Wicked, Clare bleakly speaks of how her parents treated her — and how she now knows she is no better. (She no longer has her baby with her.)
Also, in the same episode, one parent deliberately abandoned his children in the woods, and others appear to have at least neglected to protect their children from the Wicked Witch.
The web comic Cwen's Quest starts off with the main character's father throwing them off a cliff so they won't eventually fight with their new sibling. The main character's mother is never mentioned in the series.
Something Positive manages to mostly avert this except in the case of Jason's dad. The exact story of what happened is never explained but apparently at some point he ran off and left Mrs. Pratchett to care for Jason and his sister alone.
The Noob parodies this role-playing cliche, when every role-player in the guild has the same tragic past, of having their family raped and murdered by the evil hordes. Cue a cutaway to said evil hordes, who are holding a list of other farms they still have to do today. One of them is so exhausted, he asks if they can at least skip the raping.
Guttersnipe is a comic about an orphan girl that parodies "Little Rascal" style films.
Inverted somewhat in Misfile. Before the misfile, though he lived with his father, Ash didn't have much of a relationship with him, and had no contact at all with his mother. After the misfile, Ash is shocked to find her father now dotes on his daughter, and that she had reestablished a relationship with her mother.
Flik's mother in Para-Ten seems to make a habit of this.
Captain Broadband has an unnamed sidekick whose parents seem to have no trouble leaving him home alone for long periods of time to go on holiday. They pay a rather unnecessary price when they get home to find an eight foot, three hundred pound man having moved himself in without permission.
Alexander Hamilton in The Dreamer. His dad left his family when he was ten or eight years old, and two years later his mom died of yellow fever.
Oddly rare to be played straight in Jack, which deals mainly on death and the afterlife. When present, it's often played with.
The main character Jack never had parents due to having been created in a scientific experiment; same goes for his love interest Jill.
Little Megan in a late 2010 arc is stopped in time, thus unable to grow any older, yet lived with her parents until a family friend in the same situation took her away to protect her.
Zigzagged with Fnar, an innocent unborn, who has two dead parents - who both reside in Hell like he does. He is mainly kept away from them, since Mama's stuck in a dangerous place, and Papa is just dangerous. Later on the trope gets twisted further in the same direction as Fnar is given another chance at life.
In The Inexplicable Adventures of Bob!, Galatea grew up in a completely unloving environment, the closest thing she had to a father being a scientist who treated her as a lab animal. When she later spawned another creature like herself, she ended up abandoning her. When they are reunited, Galatea shows deep remorse at having been just as rotten a parent as as her "father."
In Virtual Pet Planet, Benny, the rabbit, is asked about his owner, but avoids the subject entirely.
In Endstone, after Jon tricks their daughter into helping him, Kyri rescues her and hands her off to her friends so that she can go fight Jon. When they are trapped in time, the daughter grows up without either of them.
All of the Baker Street Irregulars in Mayonaka Densha seem to be missing at least one parent. Tom's mother gave him up at a very young age, Hatsune's dad disappeared when she was five without so much as a goodbye, leaving her alone with a very cold and emotionless mother, and the whereabouts of Jack and Morris's parents are completely unknown.
Jessica Queen's father is also absent, explainable though as her mother is a three time divorcee.
Gamzee of Homestuck developed his fondness for Sopor Pies largely because his Lusus was always at sea. Terezi, on the other hand, had to raise herself because her Lusus had yet to hatch.
Post Scratch, Jake, Roxy, and Dirk all suffer from an unwitting version of this, as The Condesce killed all three of their guardians. Roxy and Dirk's guardians would have died of old age long before the two of them arrived on Earth via meteor.
Jade was raised entirely by Bec after her grandfather, who is technically her ectobiological father, died when she was young.
John's mother, who he believes to be his grandmother, died when the meteor carrying him crashed into her joke shop, leaving him to be raised by his father, who is actually his genetic half-brother.
Alone In A Crowd has a particularly outrageous example. Hope's super-wealthy impulsive-gambler parents literally and callously abandoned her, although only after finishing all the legal paperwork to allow her adoption by anyone who wanted her. This event drives much of the early plot in the comic.
In Complicated Ness No one knows the fate of Ness' parents. Ness has no idea weather his parents are alive or not.
Agathaís birth parents disappeared shortly after the attack that left Castle Heterodyne crippled. Her uncle stuck around a little longer, but he too left eleven years prior to the events of the comic. Although her mother has recently come back, itís bad news since Lucrezia is also the Other.
Gil grew up without knowing anything about his parents. Even now we still know nothing about his mother. It's stronly suggested that his mother is Zantabraxus, the Warrior Queen of Skifander.
Tarvekís father was murdered (by his own daughter) and like in Gilís case his mother is nowhere to be seen. It's suggested in the second novelisation that she was killed by Anevka.