Getting a lot of beach balls Application not responding

I have a fairly complex system with 4 internal 1tb drives, 1 external 1tb drive, 1 external 1.5tb drive and an external 2tb drive used by time machine. The system drive contains 2 partitions. The partition containing the OS is 322gb with 72gb free. I havedual cinema displays and literally 100s of applications.
My system has gotten very "sluggish" with a lot of freeze ups, apps not responding and other beach balls. I've been through a couple of OS upgrades currently at latest release of snow leopard.
Do I need to format my disk and do a clean install? If I do, can I just clone the System drive and then copy apps back? Main applications are Photoshop CS5, Lightroom 3 Microsoft Office, Real Studio, Filemaker 11, and all the associated plug-ins and support apps that go along. Reinstalling them would be a nightmare.
I run VirusBarrier X6 with scans each night.
any help is appreciated in advance.
bill

I was also wondering about login items as well, but mine takes forever to restart before it even reaches the login screen, so I'm thinking it isn't a problem with that. Unless some login items start initiating before the actual login is done. My MacBook Pro is running 10.6.7 as well, but it seems fine. I attempted an installation CD startup, checked for disk repair (ok), disk permissions (ok), then tried re-installing Snow Leopard. It got so far then couldn't finish the installation.
Ok, so I just tried it again just now and it seems to be running fine again. The only thing I did was get rid of two unknown files in login items (buttonhelper or something) using ( - ), not just hiding them. Time Machine does appear to be doing some strange things, so I erased that disk and initiated a fresh TimeMachine backup.
Don't know about you, but I'm baffled...

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