The external GPS puck connects to the serial port so the scanner keeps its location up to date while mobile. But for programming and such there is no advantage to serial over USB.
About the only thing I'm aware of is Virtual Control with Butel's ARC 536 Pro.
While one could use the front/USB port, many folks found this to be unreliable for Virtual Control. The recommended "fix" is to use the rear (GPS) port instead.
I use proscan via the rear serial and program through the front. A USB relay is in line to control the DC power. I can cycle the power remotely with it. When it comes back up the rear serial provides the user interface to proscan and the front port for mass storage programming.