I’ve been plagued by poor disk performance on my Mac Pro for the past few weeks - spinning beach balls when changing applications, long delays to show directory listings in Finder, and general system slowness. Frustratingly, it seemed to be correlated directly to the number of external drives I had attached, and sometimes showed an inverse correlation with the speed of the drives (i.e.: switching a drive from usb 2.0 to firewire 800 would make things worse). Also, after some amount of time, my blu-ray burner would freeze up and lose the ability to eject the tray. I thought that latter was some sort of incompatibility with the eSata expansion card I’d added, but much experimentation yielded that it was not the problem.
Just unchecking “Put the hard disk(s) to sleep when possible” cleared up everything (many thanks to this forum thread for the tip). I don’t recall ever changing it, but it’s possible.
I guess some of the drives have poor handling of the sleep instructions, and the blu-ray drive definitely does (though they seem to have resolved the problem with the Pioneer blu-ray drive with Lion, since that’s the one I have, and it works fine after changing this setting).