I'm happy with the Delorme USB receiver. It supports both USB and serial connections. Serial can be done via the USB->Serial driver or with a serial add-on cable you purchase from Delorme or make yourself.
As far as good software for in-car use, I haven't come across it yet. SA2004 is bearable at best but definitely has a tendancy to get behind (both on screen and voice). Also voice recognition only seems to work for 30-60 minutes and then just completely goes bonkers. Mappoint has good maps and is best used as a component to actual in-car nav software (V.O.I.C.E.S. etc). Some say the AGPS add-on helps out though I'm skeptical.
On these forums, people seem to like Copilot and destinator. I've never used either so i cannot say much about them.