The only way to tell Spotlight not to index something is to have that something available first, unfortunately. A utility called 'Spotless' will allow you to globally disable it though (and other funky things)
Are you sure there's no filesystem corruption involved - have you checked it under Windows?
Just a thought - this wouldn't happen to be something previously shared off a Windows box to the Mac that you've now connected locally?
Off the top of my head, I don't know the spec of the Mini drives - they're probably 2.5" IDE or SATA (they're usually laptop-equiv drives, 4200rpm and low power).