I will start with a simplified schematic of my circuit.

My problem with that when serial is connected (pin 2 or 3 from a prolific USB-Serial port and pin 5) before 12 volts is applied to the main power circuit, the DC-DC converter (R-78E5.0-0.5) will not output any voltage. As soon as either ground or data is disconnected, it is fine and also if it is reconnected after.
Is there a simple cost effective way to isolate the incoming lines? I have heard people using picofarad caps, but does anyone have experience with this?