Are there any downsides of running OnyX in “Automation” mode? Or for that matter, pitfalls or “gotchas” from using any of the other features, or things I should be aware of after its done what it does?

The only caveat that I can think of involves rebuilding the launch services database. That will reset the programs that open apps to their defaults. So, if you have specified that another program should open a file, you'll have to reset it. For example, if you have PDFs set to open with Adobe Reader, resetting the launch services database will reset that to Preview. You'll have to do a Get Info on a PDF, select AR from the Open With menu, and then click Change All.

Thanks for the Launch Services reminder, Jon. I'm sure I would have blown right by that.

Your feedback is exactly what I was looking for. Bravo!