it's never a bad idea to maintain the native resolution and aspect ratio.
we change the output resampling: "graphics > enhancements > output resampling: area sampling" and disable anti-aliasing: "graphics > enhancements > anti-aliasing: none" for sharp chunky pixels.
upscaling is contentous and we opt for it on a per system and per game basis. the higher quality rendering can serve to highlight the lower resolution polygons and textures, especially graphics displayed in the hud.
higher than native resolutions are never worth performance issues. on weaker hardware we opt for native resolutions.
widescreen hacks are similar to upscaling in terms of per system and game applicability.
this 13m youtube video showcases a few different dolphin graphics settings.
there's many mods and tweaks that can be made on a per game basis. it's best to refer to the wiki about a specific game.