My suggestion:
Using Carbon Copy CLoner or SuperDuper (NOT Time Machine), make a full bootable backup of the entire hard drive to an external FireWire drive.
Test the clone by rebooting the computer from the external drive.
Then trash the folder you don't want from the main computer, reboot, and run for a while to see if everything works as normal. Try running all applications and routines, but don't do any major work you wouldn't want to lose.
If there are no problems your next clone can be from the main computer, sans the folder you trashed.
If there are problems, clone back from the external drive.
That's one of the many big advantages of having a
bootable clone.