Sounds like the drive to me; I can't imagine anything else clicking inside the MB unless it's sparks and capacitors popping - and you would notice that like the dickens.
I don't bother backing up apps. I have the install disks, the serial numbers are either with the packaging or in my email for download purchases. It's about photos and music.
To put it simply, why use back up space for an app that you can reinstall?
Does anyone know a way to invoke the HDD sleeping on demand? This would guarantee it's the drive and nothing else (but I think the chances it's something else are slim to none)