Karma,
Your question is even more difficult than you may think. Unfortunately the axiom "Everything matters" is as true with computer-based playback as it is from more "conventional" sources. With a standard Mac using USB with a spinning hard disk, itunes, and the Mac OS you may get one result; with a solid state disk, different software, or a different interface you may get a completely different result.
Spend some time over at Computer Audiophile and I think once you get past the overwhelmed feeling you'll begin to develop a better sense of the issues and (hopefully) some direction. I'm in the process of doing that myself.
Good luck!