Miyu Shizuhara from Crescendo (JP). Her illness isn't specified, but it requires her to stay at the hospital for a good part of her route. And she does NOT get better.
Da Capo II: There is a double example in one route: Anzu. Said girl was the first to fall ill, then comes the protagonist boy's turn. They both spoon spoonfeed soup to each other when the other one lies sick in bed.
Chihiro Fujisaki from Danganronpa: Trigger Happy Havoc, who never had the strength to go out and play with others as a little girl. Except Chihiro is an ill boy, not an ill girl, and one of the reasons why he crossdressed was because he was considered "too weak" as a boy and was bullied for it, so he tried to protect himself via crossdressing. And we don't find out until we find him dead.
In Danganronpa 2: Goodbye Despair, there's Teruteru Hanamura's mother, who had worked herself to illness and exhaustion to keep the family restaurant open. Teruteru worries a lot about her health, and his desire to get off the island to find out if she's alright eventually drives him to murder.
Claudia Jerusalem from Dies irae ~Interview with Kaziklu Bey~ is soon revealed to be deathly ill from skin cancer. She is given less than a month left to live. Wilhelm notes that even though she tries to appear healthy, its nothing short of a miracle that she can do even the most basic of things in her current state. Her illness also forms a core motivation for Ludwig as he want's to save her so that he can have an eternal companion. In the end, it was not her illness that killed her. She instead sacrificed herself to stop her out of control Creation Figment from killing Wilhelm.
Played with in ef - a fairy tale of the two.: Chihiro Shindou doesn't spend almost any time bedridden or hospitalized, but she still suffers the serious consequences of having been hit by a car three years prior to the story ( the loss of an eye that she covers with a white eyepatch, and retrograde amnesia that takes effect every 13 hours), so she requires to be taken care of.
Ever17 features two: Yubiseiharukana (the You from Takeshi's path) who has a terminal heart condition and Coco Yagami who has Tief Blau.
Additional materials reveal the existence of Kirei Kotomine's dead wife, Claudia Hortensia, an inmuno-deficient Mysterious Waif who passed away two/three years after they got hitched. (In a subversion, she actually committed suicide in a desperate gambit to prove him that he wasn't as unfeeling as he thought — then again, Claudia was already dying so she wouldn't have lasted much longer anyway).
Unlike how this trope is usually presented, Full Metal Daemon Muramasa plays it for maximum family horror. The main character Kageaki's younger sister Hikaru ends up struck with heavy metal poisoning after eating contaminated fish leaving her an empty, emaciated husk that is slowly wasting away while being struck by frequent seizures, forcing Kageaki to wrestle to try and restrain her to keep thrashing from breaking her already fragile body. None of it is presented pleasant time for anyone involved. While she eventually gets better thanks to coming into contact with Ginseigo, the effect this experience had on her warped her mind, turning her into the Big Bad. Except, she never did get better. She is still bedridden and her body is still in a sorry state and her mind is shattered. The Hikaru Kageaki had been fighting the entire story was in fact just an embodiment of Hikaru's last remaining dream that she desperately clung on to.
If My Heart Had Wings: Isuka, Amane's old friend, was very susceptible to illness and at least strongly believed that she would probably die young. Though unlike most, she was always much more boisterous and energetic than delicate, with a more 'live life to the fullest' mindest.
The eponymous Kana from Kana: Little Sister. The cause of her disease is clearly stated: kidney failure. The game also features Sumako and Cana. Two of the three die.
Toko in Kara no Shoujo is anemic and spends a lot of time sleeping. She also requires some special medicine. All in all, though, it's not too bad until Mizuhara thinks it's some sort of drug, steals it and Toko ends up getting hit by a truck when she passes out.
All the main girls in Katawa Shoujo; in fact, the game started out as an attempt by 4chan to create the video game with the highest Ill Girl count possible. Though ironically enough, only the male protagonist's condition is actually life-threatening, since the heroines are all in some way physically disabled but otherwise healthy. There is one Ill Girl that plays this trope straight: Saki Enomoto from the Aprils Fool "Event", whose disease (spinocerebellar ataxia) will eventually kill her.
Key/Visual Arts has at least one, sometimes more, in every game. They use this trope so often that fans have started jokingly referring to any Soap Opera Disease as KeyAIDS.
Kanon has Shiori, who is terminally ill and prone to fainting, but constantly dismisses her condition as "just a cold". Her route further explores this, and shows that her illness is much more severe than she claims.
CLANNAD has Nagisa, who has an unnamed illness that causes her to faint often; it interferes in her daily life to the point that she has to repeat her senior year of high school twice. Her daughter, Ushio, has the same illness in the timeline where Nagisa dies from giving birth to her, though in the visual novel's True End she's stated to be healthy.
AIR has Misuzu; while she's introduced as seemingly healthy and energetic, she's later revealed to suffer from a mysterious illness which is actually part of a centuries-old curse, where she falls ill whenever she grows to love someone and they love her back. In the end, this illness kills her, both in her route in the original visual novel and the anime adaptation.
Planetarian has Reverie/Yumemi, with low battery power and unable to recharge due to planetarium's backup power supply failure just after the show, and that they're stuck in post-apocalypic Earth.
Little Busters!! has Mio Nishizono, who carries a parasol everywhere and avoids any physical activity apparently due to her poor health. She turns out to be a subversion, since she's not actually sick and the real reason she does those things is to hide that she has no shadow.
Setsumi in Narcissu has an unnamed condition. She kills herself at the end of the story.
Nine Hours, Nine Persons, Nine Doors has Akane Kurashiki a.k.a. June, who is very disturbed by the events of the game and breaks out into severe fevers at several points. They are caused by Junpei straying off the path that leads to the Golden Ending and creating a Temporal Paradox that incinerates her nine years prior. Also, most of her concern is fake, seeing as how she isZero.
Viola Cadaverini from Phoenix Wright: Ace Attorney looks like one given her pale and creepy/sickly appearance as well as the bandage on her head. She's a bit of a subversion, though, since the bandage is due to an injury that she got in a massive accident caused by her sort-of love interest Furio Tigre and it is implied that she is just a frail woman by physical nature, not illness.
Miku in A Profile as a result of a slightly botched liver transplant.
Akira's mother in Spirit Hunter: NG. Since youth, she had a weak constitution, which caused her to focus more on her studies than on any physical hobbies. This came back to bite her as an adult when she died of an illness, leaving Akira to be adopted by his aunt.
In True Love Junai Monogatari, the local artist Miyuki Tanaka has anemia and a very low threshold for either extreme heat or vigorous physical activity, leading her to pass out while on the sidelines of the swimming competition if she shows up there. It kinda worries the Player Character during their sex scene.
Jessica Ushiromiya is more of a downplayed example—she has asthma, but she's usually very feisty and outgoing, and otherwise doesn't have any other health issues that interfere with her daily life. However, early on, she tends to have very poorly-timed attacks that make her something of a Badass in Distress. It's later revealed that Jessica invokes this by partially faking some of these attacks to make herself look more helpless than she truly is in order to get out of awkward or uncomfortable situations.
Ange Ushiromiya was rather sickly when she was younger; being afflicted with a severe cold is what prevented her from going to the 1986 family conference, and in a flashback she's noted to often be sick aside from that instance.
Yuzuha in Utawarerumono, who is actually something of a MacGuffin — her brother Oboro's theft of the outrageously expensive medicine she needs to survive is the start of a chain of events which snowball into an international war.
In the third installment of the Utawarerumono franchise, it's revealed that her daughter Kuon of all people inherited the disease from her, though thanks to her father's blood in her veins, it isn't as fatal, but she'll suffer relapses from it every now and then. Very surprising considering her healthy disposition and attitude in the second game.
Sakura Oogami's boyfriend Kenichirou in Trigger Happy Havoc, as revealed by the Free Time talks. Even more so: Sakura explains to Naegi that Kenichirou was terminally ill and she never could beat him in martial arts, so he gave her the title of strongest person when he learned that he had just six months to live.It's even worse when you realize that between two years actually having passed and the Worst, Most Despair-Inducing Incident in the World taking place, there's a high chance that Kenichirou is dead by time Sakura commits suicide.
There's also Chihiro Fujisaki; see above.
In Danganronpa 2: Goodbye Despair, Nagito Komaeda is apparently this, specifically having dementia and stage three malignant lymphoma, and it's implied that his illnesses were what turned his hair white. While in the game it's unclear whether or not he's actually telling the truth about having these illnesses, supplementary materials have supported his claims.
Male lead Hisao. While the girls are physically disabled but otherwise fine, he's got severeheart arrhythmia that almost kills him in the introduction. It doesn't do him any favors when Emi runs into him in the hallway, either, and keeps being a problem over the course of the game. Especially in Lilly's route, in which he has two major incidents... and a third on the way to the Good Ending that hospitalizes him again and almost kills him.
Kenji Setou, who not only is legally blind but is speculated to be mentally ill as well. Only that he's a Large HamConspiracy Theorist instead.
Although Key/Visual Arts is well-known for its ill girls (see above), Little Busters! has two male examples and no real female examples, as while Mio is very delicate and seems sickly at first, her issues are very different. Most obviously there's Riki, the very Moe protagonist, who suffers from narcolepsy. And secondly there's Komari's older brother, who suffered a deadly disease that killed him when Komari was only a small child.
And Ryou's Second Love Kappei Hiiragi from CLANNAD, who has bone cancer. He either has to get his leg amputated or die.
Shin from Morenatsu is a sufferer of acute asthma, which has kept him from more physical activities and is the reason why he moved to the small village of Minosato in the first place after a life-threatening asthma attack he had as a child.
Hiroki from Private Nurse. However, there are implications that his sickness is at least as much psychosomatic as physiological and that he needs to convince himself that he can get better.
In Shall We Date?: Ninja Shadow, it's said that a male friend of Toshi Hijikata is very seriously ill, so much that the Manipulative Bastard Tsubaki Kusunoki tries to use a very rare medicine to sway Hijikata to his side. It's strongly implied that said male friend is Hijikata's partner, Soushirou Okita, and it's fully confirmed in Okita's own route where he collapses midway through the story and spends the last half of Chapter 5 passed out in bed, with Saori aka the Player Character taking care of him.
Shiki Tohno from Tsukihime fits into the role in two different respects. The accident that didn't quite kill him still left him with poor health and occasionally life-threatening anemic attacks. On a more subtle but drastic level, his Mystic Eyes of Death Perception growing constantly stronger means his lifespan is cut extremely short, and he's likely to die before long when his brain overloads.
, an inmuno-deficient Mysterious Waif who passed away two/three years after they got hitched. (In a subversion, she actually committed suicide in a desperate gambit to prove him that he wasn't as unfeeling as he thought — then again, Claudia was already dying so she wouldn't have lasted much longer anyway).