The best quality and easiest way to go, as well as most expensive, is to throw all the factory junk in the garbage can. From there, you run an aftermarket head unit to an amp or amps, run components in the front, delete the rears, and throw a sub somewhere, most likely the trunk.
The sound quality in a Mustang is going to suck regardless though. Between the road noise, creaks, and rattles, you can't get excellent sound. I'm bypassing my Mach 460 stuff and just running four mid-tier speakers off an aftermarket head unit. It's so noisy headed down the road that it doesn't matter. The flip side of that is my pickup. It is very quiet so I didn't feel bad about stuffing $3-4k worth of audio in it. I don't think it's worth it with a Mustang.