To start this circle off with a topic, I thought I would point out an issue that is roaming the internets. Seems there have been concerns with iTunes 7.5 and above sounding sub-par and even distorted. The problem is when a sample rate is set in AudioMidi without restarting iTunes. Apparently, iTunes and AudioMidi can independently perform sample rate conversion. When iTunes is started, it locks to the sample rate set in AudioMidi for CoreAudio. All library files are then up/down-sampled accordingly. If a user then changes the sample rate in AudioMidi, it is first converted in iTunes and then again in CoreAudio which is not desirable. Restart iTunes to lock to the newly adjusted sample rate. This way only iTunes will do the SRC and CoreAudio will leave it untouched. More info can be found
here.
Personally, all of my music is ripped ALAC so I just set it and forget it: 16bit/44.1 for output to a USB DAC. I do not have any higher rez tracks for which this might be an issue.