Good points, Calamity. I turned off cleanstretch and changed the desktop resolution to 632x264, which is the closest I could get to x256. Then I brought in the vertical height pot just a bit, so that my desktop and FE are slightly letterboxed. This seems the fairest solution, and confirmed that in Pac-Man, you can still see how many lives and fruit you have. All else looks as good as I think it will be, given your point below on vertical scale.
Sinistar is still far less than ideal, though. Again, I feel like it's got plenty of room to go left and right, so I would think it could scale up a bit. And it seems odd that it's selecting 720x480i as the resolution. I know this goes against the whole point of groovymame, but should I consider a custom ini or cfg file for it?