Here's what I recommend.
For just doing antivirus scans normal mode is fine. If your AV finds a virus or other malware that can't be cleaned (generally this is because the file is running) try again in safe mode. The advantage of safe mode is that only basic processes are running and therefore malware is easier to clean up. Also if you suspect malware is getting missed when you scan in normal mode, try it again in safe mode.
Leave System Restore on. Sometimes malware removal goes badly and it's better to have a means to go back to a working state, even tho that working state might be infected. When you remove an infection and know you have a clean machine, turn off System Restore and then turn it back on again. This will delete all your restore points, including some that may have been infected. It makes no sense whatsoever to turm off SR before doing a routine AV scan. If you have paid good attention to security the majority of scans will come up clean and so you have lost clean restore points for no reason.
Hope that helps.