Safe mode can prevent malware from actively hiding through certain kernel mode attacks such as call interception and injection, but it *will* prevent the heuristic engine from working properly.
I would certainly agree with that. However I think that we are just talking about a general slow computer malaise (whine ) here?

You could always run in both modes, but when I suspect any heavy duty malware I would tend to go for a live external medium or a HDD docking station.

I guess my main reason for going the Safe Mode route is that it pretty much has a dedicated environment so it runs faster............I still deal with quite a few older single core systems