Larry,
Sorry the file defrag didn't help.
Other thoughts from past experience:
1) Particular VSTs can cause issues - try removing them one by one and see if there is a compatibility issue?
2) Are you using any 32 bit plugins via bridging software? Always dodgy at the best of times!
3) Melodyne has been known to cause hangs in Sonar on some systems.
4) Check the default sample rate against your projects SR - sometimes a mismatch can cause issues.
5) I think the Picture Cache has already been mentioned - temporary files in there can seriously mount up!
Can't think of anything else off hand.
Mark (Chameleon Music)