GPS's often serve as a great resource to help you get around when you don't know where you're going. I've personally had it save me from complete lostness on more then one occasion, but it's also taken me astray more then once.
I think even if you're going to use a GPS it's a good idea check out your route on google maps or mapquest. Both may not send you the best way, and the GPS might not either. Actually, GPS's don't always agree with each other.
When I was driving back from Myrtle Beach there was a lot of whining in my car. My sister's Telenav gave one set of directions and my Dad's Garmin kept telling us to make a u-turn. From my understanding of the ride down the Telenav gave better directions. As we got closer to home we had to get over Staten Island to get to Long Island. I can't count how many times I've done this ride - NJ Turnpike to 440 the Outerbridge, continue on 440 to the Staten Island Expressway. Well both GPS's insisted on taking the Goethals Bridge. Well is screwed up my brother-in-law who doesn't know the route as well and he almost killed us twice. Then due to a miscommunication (my Mom was on the phone with my sister at the time) we ended up getting separated - I took the Outerbridge and they took the Goethals Bridge. I suspect that the Outerbridge was faster since I was driving a little slower to let them catch up, which they didn't do until we got home. But we all knew the roads well enough at that point that the GPS only served to confuse us all, I think we would have done better without using them.
The moral of the story, follow your instincts when you're local. You know the roads better then any computer, and the GPS is a back-up.
Have I mentioned that I have a fear of getting lost?