One of my players played a character in a wheelchair in one of my Call of Cthulhu campaigns. I made sure to include obstacles for the wheelchair in the campaign to make it more exciting. But certain actions were always more difficult for his character.
For example, during one session his character tried to sneak into the forbidden section of a library, but for that he needed to climb a steep staircase. That required a strength check to haul that wheelchair up the stairs, or he needed to crawl without the wheelchair. There were also a few situations where he needed to make a quick get away, which was more difficult for him. I added the occasional skill- and ability check (strength checks mostly), for a lot of these obstacles. Especially in a horror campaign, playing a disabled character can be very exciting.
Playing a character who is missing a leg or an arm can also make for cool character building, especially if this ties strongly into the character's backstory. I had an npc called Countess Roselyne Camille in my long running pirate campaign, who was missing an arm. She lost her arm due to her father standing up to a vile pirate captain called Karagoz, who severed her arm out of spite for not learning where the villagers were being hidden. This disability became a badge of honor for her, and a reminder to her people what her family was willing to sacrifice to keep them safe. Arguably one of the best characters I've written for any of my campaigns. And it had a very satisfying conclusion too. The players did battle with Karagoz, and brought him before the Countess to see justice be done to him. While Karagoz was being dragged through the halls of the keep, he kept remarking on the wonderful memories he had of the place. He tried his best to provoke the players, and Roselyn's uncle. But when the verdict came, it all came full circle:
Roselyne: “You’re a proud man aren’t you? Very much concerned with being known… being feared. It should come as a bit of a disappointment then that no one will ever hear what became of you today. You’re probably expecting me to maim you, like you did to me. You’re probably expecting me to do all manner of unspeakable things to you. But truth be told, I have no desire to become you… and no form of punishment that I could possibly come up with, could ever surpass the horrors of what you and your men could inflict on each other.”
Karagoz: "You are wasting your time, my men are loyal to the end", -he grins.
Roselyne: “I still remember how you held your blade at my throat, demanding that my father tell you where he was hiding the villagers. It was right here, in this same hall. It must have haunted you to this very day that he stood his ground and never told you. Well, today you are going to find out. There was an old dried up well in the center of town, leading to a small underground reservoir. There’s no way out of there. It is basically just a small dark hole. I can only imagine the terror that my people experienced, waiting down there in the darkness, praying that your men would not find them. I can’t even imagine what it would be like to be down there, with no light, and no food. I can’t even imagine what people would do to each other… but I guess you are going to find out. And once we’ve sealed the well, we are just going to forget about you, and no one will ever hear about you at all.”
With that said, Karagoz was dragged away, and thrown into the well, along with his men. They sealed the well with the statue that still stands there today, which cut off all sound from below in an instant. Roselyne then asked her people to forget about Karagoz. To never mention what happened to him. She wanted him to be utterly forgotten. She didn’t even want credit for defeating him. She wanted him erased from history.