There is always going to be conflict between 'safety' and 'convenience', and where you strike that balance is a matter of personal choice.
The basic 'optimum' setting is probably the 'out of the box' default setting provided by H+BEDV. You simply tinker with that to suit your own requirements; for example I like to have the Win32 File Heuristics of the demand scanner set to maximum, but because this increases the possibility of FPs, I also have the 'Repair' feature set to 'Record in report file only'. Thus at the end of a scan AVPE will report any findings (without attempting to 'repair' or promt me during the scan) and I will then have the chance to investigate further before deciding what to do. If the finding was not a FP, I could then go into 'safe' mode to deal with the files in question. This works for me because in practice I have very few FPs.
With demand scans I also like to have the 'Search' section set to scan 'All Files', this does increase scan times but in my case it is only an extra 10 minutes or so and I consider it worthwhile. The recommended/default setting is just to scan program files and then, only if you have an infection, go into 'safe' mode to do a full scan.
With realtime protection a different setup is required, I still like to have Heuristics enabled but set them to 'Medium', though having the setting at 'Max' is also possible. By default the Heuristics in Realtime are not enabled (if I remember correctly!) to avoid people complaining if they get FPs; but I will always accept potential inconvenience in exchange for greater safety. Obviously 'report only' has no application in realtime as bad files must be blocked. Some people like to be prompted before action is taken, but I suppose it may be safer just to set the Guard to block/attempt disinfection/delete automatically, merely informing you what it has done after the event - but it is just too bad if you experience a FP!
With regard to the 'Miscellaneous' section, you would normally have everything ticked; unless you are using AVPE as a backup scanner, in which case you would leave 'load the Guard at system start' unticked.
I'm afraid no one can advise what the 'best' settings are going to be for another person - everyone must make up their own mind. If in doubt, just stick to the default settings and you won't go too far wrong!
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