Garmin StreetPilot 2610
Since my job involves visiting 4-5 houses a day all over the Bay Area, I put one of these in my truck. With a 512MB CompactFlash card, I was able to load all of the data west of Montana/Utah/New Mexico, so I have street-level maps of about 1/3 of the US at all times. I found that it saved 30-45 minutes per day vs. trying to navigate from MapQuest print-outs. The GPS can route you correctly, and knows about things like one-way streets, so you won't THINK you can get somewhere you can't, which happens with printed maps sometimes.
It will hold a couple hundred waypoints (addresses or other locations), and you can pick one and route to it near-instantly. There is a Detour button that will find another route for you, and if you decide to leave the route on your own, it will auto-re-route you (unless you turn that feature off).
Because it uses flash memory, it calculates routes quickly and is immune to bumps and vibrations. I did find that the internal antenna isn't always great at quickly regaining signal when coming out of a tunnel, under an overpass, or whatever. I just recently picked up an external antenna for it, made by Glisson, that costs half of what the OEM external antenna costs, and it works great. Signal recovery takes no more than 2 seconds from leaving a tunnel, and in other situations, may not lose lock at all due to picking up sats off the horizon.
It would be hard to live without it now.
-Troy