I think there are a few features in the Settings menu related to the nav features that you will not be able to access unless the parking brake is on, but the entering of addresses and watching ipod video are the main ones.
I was kind of surprised to find out that if you install a rearview camera with the system, the video feed for the camera is available while you are driving down the road at any speed. It's kind of fun and interesting, but from a safety point of view is probably just as distracting as watching a video on your ipod while driving.