I have had problems with iTunes with a large library on a FW drive, but it was mostly skipping and just problems with audio. Nothing serious.
This was a while ago, and since 10.3.3 (i think) it has been fixed. I haven't checked since then but there were a LOT of Apple Support threads about it back in September when I started having the problem... I'll see if I can dig it up...
my posts on the subject (actually, ALL of my posts PERIOD) are GONE...
Freakin Apple! Apparently they purge the archive every 90 days or so!!! WTF! that makes no sense!!!
well, nevermind then...