Dot Flow/WMG

Sabitsuki's computer houses some sort of supernatural entity. (Plenty of unmarked spoilers!)
It's never explained just what happens when Sabitsuki sits down at her computer. Does she doze off? Space out while browsing? Surf really disturbing websites? Or perhaps it's something much more sinister: .flow (though this may not be its real name) is actually an intangible demon or monster that is drawn to humans that have Sabitsuki's illness and interacts with them through their favorite pastimes - a computer in Sabitsuki's case. It is able to draw the user into a trance, and opens up their mind to explore their pasts and fears, the whole experience coming off as a really strange and disturbing dream. Furthermore, the user will always feel compelled to return, their will to leave their homes weakened by their disease and .flow's influence. The endgame is .flow taking over, influencing her to surrender all of her effects - everything that made her Sabitsuki - as she reaches the end of her life, thus giving up what little strength she had and causing her to lose sight of herself, simply becoming "Rust." .flow is only just waiting to unleash itself onto the real world to finish Sabitsuki/Rust off for good. It wants to wait until Sabitsuki/Rust is ready to go outside to look at the world one last time, delivering the crushing blow just before she's ready to let go for good.
 * The effects are representations of Sabitsuki's inner self, and reminders of her past (the uniform and black hood, and possibly the steel pipe, handgun, and whistle), fears for her own future (the ghost, viscera, corpse, tumbling doll, gas mask, and possibly the dress), things she enjoys (the cat, broom, headphones, and possibly the diving helmet), or simply random moments of make-believe (most other effects). They could be considered a symbol of her remaining mental strength, as .flow ultimately wants her to give them up.
 * A few, like the cat, ghost and broom, let Sabitsuki travel through her mind more efficiently, inadvertently letting .flow get a better look, as well.
 * Characters like Smile are memories of former classmates, horribly twisted by .flow. The doctor and nurse were the ones who oversaw her hospital stay, while the maids may represent other caretakers, wearing gas masks (medical masks in Sabitsuki's real memories) to keep themselves from becoming infected. Some, like Oreko, are the few that Sabitsuki is managing to keep mostly intact.
 * The Kaibutsu are .flow's way of showing what eventually happens to anyone who interacts with it. Should Sabitsuki attack the Kaibutsu in an attempt to deny what's happening to her, they retaliate, so as to crush her spirit even further (sealing her in a room) and tell her that her fate's been sealed (killing her).
 * The worlds are more reminders of her past. Most prominent are the hospitals, bringing to the forefront Sabitsuki's illness and a traumatic childhood of seeing many other children die around her. The school was where Sabitsuki used to hang out with her friends until she became too ill to go anymore. There are also lonely city streets, dark alleys, dingy apartment buildings, creepy overgrown gardens (possibly hospital courtyards, given the presence of sick children in some of them), bars, sewers, nightclubs, piers and the ocean, and cold snowy factory areas - all places in or near Sabitsuki's town.
 * The famicom world is based on her memories of video games she played as a child, and still plays to pass the time to this day.
 * The flesh-walled world is .flow showing Sabitsuki the state of her own body corrupted with germs (red demons) and with a weakened immune system (the black-haired girls dying off). The microscopic world is a look at the ill but strangely serene state of her cells as they succumb to the illness. Eventually, the red demons break out into other areas, diminishing the last of Sabitsuki's health.
 * The world known as Hell is .flow taunting Sabitsuki, saying that that's where she's going to go when she dies. The industrial maze and the rusted picture world are meant to be confusing and claustrophobic, as well as dangerous due to the plethora of hostile Kaibutsu, weakening Sabitsuki's resolve and instilling feelings of despair and fear.
 * The prison could represent a feeling of entrapment due to Sabitsuki's illness, perhaps meaning that her hospital stay felt more like a prison sentance; could be a reminder of some past crime (possibly committed with a handgun or steel pipe...) that she may or may not have been caught for; or it could be .flow telling Sabitsuki that she is, effectively, trapped and cannot escape no matter what.
 * The rooftop ending (keeping the effects) is Sabitsuki holding onto the last shreds of herself and leaving on her own terms before .flow can get to her.
 * The maid ending (surrendering the effects, but not finding the empty boxes) is .flow corrupting Sabitsuki, turning her into Rust and killing her off, possibly drawing her into itself via the maid to torment her in the afterlife.
 * The true ending (surrendering the effects and finding the empty boxes) is .flow corrupting Rust, but not before Rust manages to delve deep and discover the last hidden corners of her mind. She finds and kills off the corrupted part of her, gaining some control back. .flow is ready to kill her, but is not anticipating one last bit of ferocity on her part, as evidenced by the maid backing away in fear. Rust is attacked and killed, and put on display in the dream world, but manages to escape and ultimately remember herself as Sabitsuki.

Sabitsuki is an adult, and her room is a prison cell.
Having grown up in unsavory slums (hence all the urban areas), she was a lowly thug who "bit off more than she could chew" after a messed-up coup that unexpectedly ended in one, or perhaps multiple horrific murders (explaining the steel pipe and handgun -- the Kaibutsu's faces immediately brought blunt trauma to this troper's mind). "Smile" may be an accomplice that betrayed her, or even a representation of her thug self. Some time during her bail, she contracts what is possibly a brain disease; it's taken a solid foothold and she's already fairly delirious by the time the game starts, and the Erosion Counter represents the stress of each event aggravating her condition. As for the computer? No idea.

Sabitsuki is some weird test tube baby.
And a unstable one at that

Sabitsuki had her family murdered in front of her
was a representation of that, with the big blue girl being Sabitsuki's mother, and the rest being her sisters.
 * There also, if I remember, is a hard-to-find world that is white, where abunch of blue girls stand around a dead blue girl.

The red demons and the Kaibutsu are competitive brothers and sisters
The Kaibutsu are, apparently, according to lol, officially female. The red demons don't seem to have a gender though, so let's assume they are male. The reason they replace each other is because they are fighting siblings, and they want to prove they can be better.

The cake in the Sugar Hole is made from human flesh
Which is why Gabe, the bar Kaibutsu,, which is actually an oven.

Sabitsuki's family was part of a cult
The  was actually some ritual her family did where they kidnapped some people and tortured them.
 * Smile and Sister's mother was one of the people who was tortured and killed by Sabitsuki's family rituals, which is why they act nervous around her, and
 * The room that neither Sabitsuki nor Rust can enter is something that was full of something horrifying, and so she cannot remember it.
 * This broom stick's magic was taught to her by the cult leaders.

Sabitsuki is a cosplayer
Her favorite thing to cosplay is Kiki from Kiki's Delivery Service.

Oreko is Sabitsuki's only friend
There is actually a friend meter, and certain specials are unlocked if Oreko is visited enough. Plus, Oreko trusts Sabitsuki enough to give her a diving helmet to help her come back.

Gabe isn't a Kaibutsu.
He doesn't appear to have a bleeding face like the other's, and he uses a weapon instead of sending people to the inescapable area. Also, instead of chasing people around, unless he is attacted, he is pretty calm and just seems to enjoy having drinks at the Sugar Hole.
 * He does get a bleeding face.

The Gas Mask Maid is a sick woman who has fun torturing children, and her alias she tells to the children is "Parade"
Which is why, when you go up the elevator, there is the word "Parade" written in blood, and the elevator leads to suffering children. It is also extremely near the Sugar Hole. Sabitsuki escaped from the "Parade house" when she was younger(Which is why there is a young Sabitsuki in a room), and so, for
 * The maid costume is a disguise, so is the gas mask. Her true form is Viscera,.

Sabitsuki is a Kaibutsu which hasn't been made hostile
Hostile Kaibutsu get more bloody faces, which can be pressumed that sane ones don't. Sabitsuki is perfectly sane in comparision, so she doesn't get bloodied... .
 * Although, the Kaibutsu's actually DO have a mild amount of blood on their faces, even the sane ones. Although, because of the Kaibutsu in the Corrupted School event, this could be true.

Smile represents Monoe
Monoe only unnervingly smiles, and Smile does too. And, Monoko is said to be Monoe's little sister by some, and Smile has his little Sister as well.

Sabitsuki's in a coma. Sister and the black-haired girl are the same person.
The entire game is a dream of Sabitsuki's as she lingers on life-support. This (sorta) explains why she uses her computer instead of her bed to access the dream world - because she's already asleep. The beginning and ending of the game, which both feature Sabitsuki floating in a black void, are meant to hint at this.

As for what put her in the coma, my theory is that Sabi used to be in Smile's gang, but decided to quit. In retaliation, several other members of the gang jumped her and beat her severely enough to leave her comatose. Sister, who was hanging out with Sabitsuki at the time, attempted to stand up to the attackers. Not knowing she was Smile's sister, they beat her up too. Whether or not Sister survived, I can't say, but she WAS horribly disfigured in the attack, which is why the black-haired girl's hair is always hanging in her face.

Sabitsuki blames herself for this. At the end of the game she sees Sister die over and over again, and then literally beats herself up over it.

The gas-mask maid killing Sabitsuki at the end is symbolic of her being taken off life support.