The first Sims game used 3D character in a 2D isometric scene. As far as I know, they used depth maps for the 2D images, to define which part of the 2D should be in front of and behind the character. Though it's probably easier to do the whole game in 3D now, than do it this way. :)
What you could do is realtime render 3D models of the characters to images/sprites in the background, that way you can change clothing, hair, weapons and so on, while still using 2D in the actual game. It shouldn't take more than a second to render out new sprites after you change the look of the character. I did a test with this in Blitz3D a while back, though I never used it and have no idea where I put the code. :) It's quick to code though.
What you could do is realtime render 3D models of the characters to images/sprites in the background, that way you can change clothing, hair, weapons and so on, while still using 2D in the actual game. It shouldn't take more than a second to render out new sprites after you change the look of the character. I did a test with this in Blitz3D a while back, though I never used it and have no idea where I put the code. :) It's quick to code though.