Applications freeze and will not force quit

Model Name:          Mac Pro
Processor Name:          Quad-Core Intel Xeon
Processor Speed:          3 GHz
Number Of Processors:          2
Total Number Of Cores:          8
L2 Cache (per processor):          8 MB
Memory:          4 GB
Bus Speed:          1.33 GHz
Mac OS 10.5.8
My Mac has been in the shop (Genius Bar) 4 times in the last several months for an array of problems. They've diagnosed and replaced a broken riser and diagnosed (and I replaced) a defective 2nd back-up internal drive. I've also moved my large library of fonts (I'm a designer) to an external drive and now use Font Book to very gradually add only the fonts I'm currently using. Yet there is still the lingering problem that periodically an application will freeze and refuse to force quit. Some other applicatons may still be working fine. I cannot reboot; if I try to restart from the menu bar it disappears and the whole system freezes. So I have to turn it off with the power button, wait a minute and then start up again. This happens several times a day, although I am at times able to work fiveours straight with no problems.
[I've repaired permissions and zapped PRAM countless times.] 
I'm now convinced there must be a software problem/conflict. But how the **** do I figure out what that is?
Oh, and of course this is all happening when work is insanely busy. HELP, please.

Russell Pond wrote:
The only pattern I can see is that it seems to lock up when an iPod is mounted or mounting. There isn't any problems just opening iTunes and listening to music. But, mounting devices seems to hang it up.
Any thoughts, or solutions?
Try plugging the iPod into a different USB port - does it continue to freeze iTunes?

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