How about a game that focuses on handicaps?
It doesn't focus on one gimmick or just lowering stats. That's been done.
I'm talking about limited chroma or luminance vision. Or even blindness. Deafness too, but people might be overly used to playing silently. A lot of games have visual cues though. With the game, it would give you an objective and one or more handicaps you have to overcome to finish the objective.
Some things would naturally be hard, like blind dungeon navigation, or playing an instrument by ear with tone deafness. But, certain objectives would be purposefuly hard. Like, not being able to see colors and most of the graphics are different colors with the same luminance.
Some of the harder objectives will involve Deaf/Blindess or Synesthesia.
I don't know how fun a game where you are forced to take on handicaps would be, but hopefully my horrible typesetting and grammar skills will save this post.
Also, because of all this, the game would be playable, for the most part, by people with almost any handicap. By forcing every game player to overcome handicaps, it also lends itself to b played by game players with handicaps.