Normally you don’t need to touch anything, except possibly line multiplication (under Output Options), default is 2x so only 480p output.
Also I would recommend most users to try passthrough with their 480i/576i sources (default is linedoubled to 480p/576p), to see if it looks/feels better to them. http://junkerhq.net/xrgb/index.php?title=OSSC
Yes, passthrough does look better there as I discovered with my PS2. I found a page that lists optimal timings for different systems. Do those make the picture any better on passthrough or only with line multiplication?
If you are overwhelmed by menus, then I would wait a bit with optimal modes.
Whether it looks better or worse is personal preference. I like the normal modes because with scanlines and some scaling by my display it looks more ”natural” (I tend to use x4 mode).