The best way is to run the audio through your car stereo - using the bluetooth audio interface to the car is best if you have a car with that (though it too sucks power). With modern bluetooth enabled cars with built-in mics, the phone remains fully able to process calls.
Originally Posted by NickM99
A less slick way is to take the feed out the Pre's audio jack to either a line level audio in jack on the car (common on vehicles and radios from 5 years ago) or even to an audio cassette adapter. This is a bit of a mess should you receive a call while plugged in as you will hear the caller but they will not hear you until you unplug. The Pre's headphone jack can also become stuck such that it doesn't recognize when you've unplugged it - there are various ways to "unstick" it should this happen (including simply using a slightly more robust headphone jack like a Blackberry headphone) but this usually only occurs once every 50x's. I use a headphone adapter to cassette deck adapter in my old hybrid car and bluetooth in my new one and vastly prefer the bluetooth arrangement but you work with what you've got.
In the hybrids, while on electric-only drive a low speeds, the Pre's speakerphone is sufficient. Out on the freeway, the air turbulence raises the background ambient too much to make the Pre's built-in speakerphone intelligible. In my experience, high winds, heavy rains or even a full blast defogger running will also outshout the Pre unless you run it through the car stereo.
I do a lot of driving in my job. I've listened to thousands of hours of podcasts with Dr. Podder/Guttenpodder, and use Sprint Nav (or my new hybrid's onboard nav) when I am in a coverage area and Navit when I drive outside it (which is for Sprint is almost all of rural California, including the northern forests, the coastline, the Sierras, etc). I used to keep my old Treo in the trunk loaded with TomTom maps for when I drove out of Sprint Nav's range. Since I began to use Navit on the Pre, I no longer need to lug the Treo around. It has improved a lot over the last couple of years and aside from the funky address entry interface and the glitches in OpenMaps for US cities, it works great.
For power, you are going to need to plug it into the car for a trip of any reasonable length. Unlike telephone usage, where the screen blank between calls, in GPS usage, the screen is on, the GPS locator is running, the audio is running and the processor is updating your current map location and re-routing on the fly. This all takes power and will quickly drain even a 2300 mAh battery on a multihour trip. Either only run Navit in the areas you are unsure of, or plug it into the car using a cigarette lighter to USB adapter, or in a new car, a direct USB port. When plugged into an external power source, the screen can remain fully lit, which is useful when driving in daylight.
Good luck and go out and enjoy your new navigator tool.