A quick follow-up.
I do not have any metrics but both calibre and the viewer open definitely faster after excluding the calibre temp dir from an antivirus real time scanning.
But it looks like you have to point both TMP
and TEMP environment variables to your calibre working directory. I guess this is because the application, some places looks after TMP and another after TEMP.
But hey, this is the best app I've gotten my hands on in the latest couple of years.
It would be great though to be able to configure this in calibre, like the way you can choose where to place your TIF folders in IE.