I used to be scared of The Legend of Zelda. It was the kind of delicious terror that you feel when you cover your eyes during a scary movie and peek through your fingers. There were no walls; I could go in any direction, but there were no signs to tell me which to take. (The original Mega Man had the same effect on me, but in a different way). Without the tunnel vision of Super Mario Bros., I tread carefully up a river, across a bridge and into a tree. "I found the first level!" I thought, reading the upper-right corner of the screen. And then, "Wait a minute. I don't find things."
A lot of games I like are about running around finding things. Although I only know where a few places are in my town and go everywhere else with my mother or a friend, I've remembered the layout of Hyrule in A Link to the Past without having played it for years. While I have a lot of trouble navigating 3-dimensional space that I'm physically in, it's much easier to find my way around a 2D expanse on a screen.
Neuroscience and the MRI I had when I was 12 can tell you why. I have some periventricular leukomalacia (PVL), which is a fancy Greek term for "some white matter around the brain's ventricles has died." Because of the skillset I have, I've also been diagnosed with nonverbal learning disabilities (NLD). Most of the dead white matter is in my right parietal lobe, which is a mapmaker: it makes maps of where one is in external space, and internal maps of one's body parts--particularly the left ones. So people with right parietal damage can lack awareness of the left side of their bodies, as well as the left half of space. They can also have trouble with spatial orientation in a more general way.
My spatial cognition is good for some things, bad for others. I interpret an object seen from different angles as being several different things. This kind of thinking is handy for distinguishing letters: recognizing one shape flipped four ways (b, p, q, d) as four separate objects. But letter-vision is not good for recognizing a building that looks different to you depending on how you come to it.
Letter-vision is better—not good, but better—for video games. They exist on flat screens, in two dimensions; no matter how advanced the graphics engine is, a building in a game cannot be seen from as many perspectives as it can in real life.
I play a lot of slower-paced games with lots of text. As a kid, I thought Dragon Warrior was the coolest game ever because almost everything I did--walking down stairs, opening chests, fighting monsters--I did in writing.(I lied; letter-vision is good for video games).
First-person shooters are hardest for me; I don't know if it's the illusion of maneuvering my own body through space, as opposed to controlling another person remotely, or what. I do like a couple, though, including the BioShock demo. And I've got my eye on this cool one-button FPS contest.
A lot of computer games are more difficult for me than console games. Because I'm not fully aware of my left side, it's 40% weaker than my right (the fancy Greek word for such weakness is hemiparesis) and not all the fingers on my left hand are mapped correctly to my brain. My middle and ring fingers are tied together somehow. While I learned to type, my fingering is unconventional; though I can type "was" and "sad," I have a much harder time using those letters to maneuver someone. It's better if I can map movement to the arrow keys and use W, A, S and D for stuff I don't need as often, or as all-at-once. For this reason, I like games that can be played just with a mouse. Yes, I am drooling over Diablo III. And playing the Hello Kitty Online beta. (Hush). Similarly, I like Games for Windows titles that have support for XBox 360 controllers.
When I have disability-related problems with a game, what I want is more options. I want to do things differently than the way a game is forcing me to do them. One the one hand, the multisensory nature of games seems well-suited to give players this customizability. But on the other, it seems a lot of creators think of their game's multisensory experience as a package deal: we need all that sensory input to play. There really is authorial control in games, and to be more accessible game makers will have to let go of some of it.