Hi, so82. It generally isn't necessary to scan with Ad-Aware SE in safe mode. However, if you are having trouble removing a detected object, scanning in safe mode may indeed help as the object will not be loaded in safe mode, thus more easily allowing Ad-Aware to remove it. I am not aware of specific objects that Ad-Aware can more easily remove in safe mode. However, for serious infections, a full system scann, followed by a scan in safe mode are frequently recommended. Depending upon the circumstances, another method recommended is a command line scan with +procnuke.
Should you have problems removing an object with Ad-Aware, please don't hesitate to post a logfile.
Please let us know if you need further assistance.