Some games can be modified at a global level to modify the difficulty of everything in a game. In assist mode, enemies could have fewer hit points, obstacles could be more forgiving, the player could be given more time, etc.
Modes of Play
For some players with mobility or cognitive issues, gameplay that requires quick or precise movement can be too challenging or physically painful. Include other modes of play that aren't time based, like puzzle mode.
The Grand Theft Auto series lends itself well to accessibility simply because its open world offers lots of different ways to enjoy the game. Simply walking around is fun in and of itself.
For players with hemeplegia or hemeparesis, who only have use of one of their hands, using two thumbsticks to move their player and the camera is an impossible task. Supply them with assist modes like auto-aiming and automatic camera movement so they can play your game.