Charles Francis Xavier (also known as "Professor X") is one of the world's most powerful mutants, a very effective telepath, as well as a scientific genius, and globally respected expert on genetics and mutation. Xavier is typically depicted as a paraplegic confined to his iconic wheelchair, though, the actual reasons for his disability are rarely discussed.
In the film X-Men: First Class, a misdirected bullet into the spine fells Xavier and is the cause of his later handicap. However, in the comics, he is crippled by the alien Lucifer, who is on Earth while doing some scouting for a potential future invasion. Which feels kind of clumsy for an invading alien race, sending individuals down ahead of the rest of the group to drop stones on powerful telepaths. Just stay on the mothership and nuke us from orbit, right? Who's with me?
While trying to save a blind man from an oncoming truck, Matt Murdock is blinded by a radioactive substance that splashes on him. Let this be a lesson to all of you: never try to help people. Fortunately for Matt, though he could no longer see, the radiation heightened his other senses, giving him the human equivalent of a bat's sonar and making him fairly tough to kill in a fight, as a series of B-level Marvel Universe villains - including such kind of almost memorable adversaries as The Owl and Stilt-Man. (Has there ever been a less menacing-sounding comic villain than Stilt-Man? Shouldn't be too hard to knock him to the ground, right?)
Daredevil's blindness did cause him one enormous disadvantage, however - the inability to pick out a halfway-decent looking costume. He started fighting crime in his father's yellow-and-black boxing robes, looking more like "Bee-Man" than a Man Without Fear (as Daredevil would come to be known). Later, he settled on this red leather number that makes him look kind of like a cartoon devil that ran off to join Cirque de Soleil. If Batman's persona is designed to strike fear into the hearts of villains, perhaps Daredevil's throws them off-guard by making them think they've stumbled into a fetish club? If so, mission accomplished.
After retiring from being Batgirl, Barbara Gordon was sought out by The Joker in Batman: The Killing Joke. The Joker ends up shooting and paralyzing Barbara in an attempt to drive her father, Commissioner Gordon, insane. A version of this story was told on short lived television show "Birds of Prey." Barbara doesn't let her handicap let her down, and continued to fight crime a different way, by serving as the head of operations for the Birds of Prey team, renaming herself Oracle.
Years later, Barbara got back in the Batgirl costume, fighting crime how she use to, when DC rebooted the comic universe. The events of The Killing Joke still happened, and she still became Oracle, but rehabilitation was her friend this time around.
Captain Marvel Jr. was introduced to the Marvel Family of superheroes in DC Comics back in the '40s. (Yes, he's a DC character named "Captain Marvel." Not to be confused with the Marvel Comics character "Captain Marvel." And they wonder why people who don't read a ton of comics sometimes find them inaccessible!)
Initially, he was a newsboy named Freddy Freeman who dreamed of one day moving to Santa Fe before starting a labor movement against the greedy Joseph Pulitzer. Actually, hang on, that's the plot of Newsies. Freddy Freeman was a newsboy who, while on a fishing trip with his grandfather, got caught in the midst of a battle between the original Captain Marvel and Adolf Hitler's favorite superhero, Captain Nazi. (Can't imagine why THAT character ever faded into obscurity.) Interesting side note: there was also a character named Bulletman present at the time.
Anyway, granddad dies, but Captain Marvel is able to save the now-crippled Freddy by taking him to see the wizard Shazam and transferring some of his powers into the boy. Freddy could now turn into the non-disabled superhero Captain Marvel Jr., though his Freddy persona never fully healed and walked with a limp for the rest of his life. Who knew Shazam was such a troll?
Originally, Cable was introduced as a dangerous, shadowy figure without a past, drafted to join the New Mutants as part of their struggle against the Mutant Liberation Front. (Weird, I thought they were the People's Front of Judea...Or the Judean People's Front. One of those.) In the '90s, we got a bit more of a sense for his past, including that he was born Nathan Summers and was the son of one-time X-Men leader Cyclops and Madelyne Pryor.
But what was his disability, aside from a cripplingly complicated backstory? Well, Cable has a number of "techno-organic" body parts, you see, including a mechanical eye allowing him to see a wider range of light waves than normal humans and a robot arm. You know, like Daft Punk.
Unfortunately, he also from a "techno-organic virus" (as one does), which definitely hinders his ability to use his mutant powers, not to mention his general control over his own body. Perhaps this is why the installation of mechanical robot arms is not covered by most standard HMOs. Tragically, in 2010, Cable succumbed to the virus after straining himself to open up a time portal. So it goes.
Silas and Elinore Stone might be the worst parents in comic book history. First, they perform a variety of scientific experiments on their own son, Victor, trying to boost his intelligence. Later, he's hanging out with them in their lab when their teleportation experiment goes wrong, unleashing a huge gelatin monster into our world that proceeds to viciously mutilate him. Silas manages to save Victor's life by...wait for it...covering his entire body with experimental mechanical prosthetics and metal limbs.
They didn't even get him to sign a waiver! Nope, just open portal to a new dimension, flatten first-born son, then cover him with twisted, potentially carcinogenic gadgetry and send him off into the world to inspire horror and sadness in all who see him. Where do we send the "World's Best Dad" T-shirt again? (Presumably not to his lab...what with that whole gelatinous creature from another world thing....)
The Chief (Dr. Niles Caulder)
As a young man, Niles Caulder was a brilliant engineer and scientists dedicated to coming up with a formula for prolonging life. He created a sort of immortality chemical with funding from a mysterious benefactor who unfortunately turned out to be the evil, immortality-obsessed and highly appropriately named General Immortus. After discovering his employer's true intentions, Caulder refused to continue his work, and Immortus responded by implanting explosives into his body, which is kind of a harsh management style. But effective.
Caulder succeeded in removing the explosives from his body, but at the cost of his ability to walk. He would spend the rest of his life in a wheelchair, though this did not stop him from rising to a leadership position in the superhero team, The Doom Patrol, where he came to be known simply as "Chief."
Doctor Mid-Nite, introduced in 1941, was the first blind superhero, predating Daredevil by over twenty years. Plus...he's a REAL DOCTOR. The character has actually been embodied by 3 different heroes over the years, but was originally a surgeon named Charles McNider.
McNider was operating on a witness who was scheduled to testify against the mob when someone tossed a grenade into the room, blinding him. During his recuperation (which in 1941 presumably involved a lot of eye bandages and moaning), he discovers that he can see again, but his vision is inverted. So he sees perfectly in total darkness, but nothing in bright light. He decides to use this peculiar ability to fight crime, along with his new owl friend, Hooty. (His other disability? Inability to come up with clever pet bird names.)
Echo (sometimes called "Ronin") appears frequently in Daredevil comics, and is a rare deaf superhero. Born Maya Lopez, she was raised by the villain The Kingpin, who had killed her father, but not before promising to raise the child. Her deafness proves to be both an asset and a hindrance, giving her amazingly fast reflexes and the ability to mimic other people's movements, but also making her ineffective in dark areas and unable to communicate directly with allies mid-combat.
Once she's all grown up, Echo begins dating the blind Matt Murdock, not realizing that he is her adopted father's arch-nemesis, Daredevil. Also, apparently not realizing how hard it is to learn sign language when you're freaking BLIND. "No, make your hands to this. No, THIS. Like a letter 'J' looks. Argh!"
Marvel's 1975 response to the blaxploitation was this badass lady cop character, a sort of comic book take on Foxy Brown, or Cleopatra Jones. Misty was an officer with the NYPD who lost her right arm after thwarting a bomb attack. Tony Stark (the alter-ego of Iron Man, duh) was able to fashion Misty a bionic arm which gave her super-human strength, allowing her to crush pretty much any object in her fist, and punch with intense force. In later years, the mechanized arm was even upgraded to near-indestructable adamantium, and enabled her to turn it into a freeze ray, and even control a robot army with it. Not too shabby.
Important to bear in mind, though, that the rest of Misty is not bionic, or enhanced - just the arm. So she can't really lift heavy things, which would require lifting with cybernetic legs and back. So in the end, her armlessness was less a disability than a future super-ability. There's probably something kind of uplifting there, if you work at it.