As for GM:S, I find the best way to handle upscaling is to have the viewport be the same size as the view in-game, and then change the size of the window to an integer multiple of that (with code on run-time in the first room's creation code)... this keeps the application surface pixel-perfect, but stretches it to cover the larger window. If you have graphics interpolation turned off, it's drawn without interpolation, and as a result you get crisp crunchy pixels <3
(Also, if you remember the "lines between tiles" issue, this way to upscale graphics also resolves that)