>and oftentimes the graphics are upscaled to match the game resolutions, which will sometimes clash with non-upscaled pixels
I phrased this a bit poorly, but what I'm trying to say is that sometimes the sprites will be, for exemple, 16x16, but the game itself will be something like 1280x720, so the sprites will get upscaled. If the game has non-upscaled pixels in its graphics (this is common in particle effects, for exemple) they will clash with the upscaled sprites.