In terms of set up, a few key points (for those using OSX):
You have one 'iSyncer profile' per disk (you can partition disks and manage multiple profiles)
The software doesn't appear to like either Smart or Genius playlists - if using those iTunes functions, create the list, highlight all tracks in that list and then create playlist from selection; this replicates the automated list in manual form which is then read by iSyncer
What I did:
I partitioned up a 32GB USB flash drive into two 16GB drives using one for straight transfer of MP3 (800 tracks of my most played music initiated from a smart playlist) and the other for transfer of a converted set of MP3's files - MP3's to FLAC (a selection of CD imported top quality / favourite albums)
This lot takes up just over half of the Mini's hard drive. If you double up tracks in various playlists they will be imported multiple times onto the cars hard drive - this therefore means you need to make sure you don't have duplicates in your playlists before syncing.
Those that have explored the functionality will know that if you update playlists you essentially need to format (delete) the cars hard drive and then re-import each time you update the playlist otherwise you simply end up doubling up each track. Not perfect but not overly onerous....
I have seen it written else where but can now objectively confirm that music imported to the cars hard disk is of notably better sound quality than that played direct from USB, USB cable connected phone or Bluetooth. FLAC files sound great but do take up significantly more drive space (roughly 3 to 4 times that of 256kbps MP3) hence why I have used FLAC selectively on good albums originating from good quality CD imports - essentially files that warrant full decompression, not those that have previously been compressed and expanded.
Anyone toying with the Harmon Kardon upgrade who has even a passing interest in music should go for it. My subjective perception is that it equals the sound quality of BMW's Individual Audio systems that were optional on the last generation of high end cars (I owned one such car in the e61 M5).
ISyncer is the best way I have found to work with selected tracks and the cars hard drive. If you leave the data on a plugged in USB drive you retain full playlist functionality with the ability to update at will as if the USB drive were an iPod (you do though lose the ability to have your phone plugged in at the same time) - as I said before though, my subjective view is that hard disk stored music is a better reproduction but others would argue that point.