If it is an issue with the Finder, then it is likely going to be in
~/Library/Preferences
... not with permissions (which looks at /Library/Receipts and could deal with a bad mouse or usb cable, but most likely something that looking for corrupt plists might find, or a new user account; sometimes just move/rename the Preferences folder helps. And I would use Applejack to delete the cache folders, always a likely source for problems and corrupt files and very active.
Hardware issues or changing hardware can result in corrupt nvram in which case a single or dual boot of PRAM/NVRAM reset is enough, or quicker still, a trip into Open Firmware (cmd + opt + of) will do the trick with
reset-nvram
set-defaults
reset-all
... and I find quicker, but only when adding or changing PCI, RAM or disk drives.
If you use 3rd party mouse driver (USB Overdrive) then look in that direction.
I had a folder with 1000 items. No trouble. Let it grow to 2000, and still no trouble. But around 2400+ it would just cause the Finder to beachball if I tried to save to that folder, until I broke it down into smaller sub-folders of 500.
Disk Warrior 4 would be another tool to scavenge your drive for files and directory issues (Option click on the Repair/Rebuild button does a more thorough read of the hard drive's contents).
MacFixit has some excellent tutorials and 3 yrs of tips on CD even. There are a plethora of FAQs, too.