I've had Navigon for the last year or so. In fact, I have driven to from FLA to NC, FLA to NY and vice versa at least twice with it. It was purchased before there were region specific apps.
It has always been reliable and given correct directions. It actually has rarely thrown me a problem.
Assuming you are in the US and don't plan on going across county any time soon, I'd strongly suggest Navigon Region. Heck; even if you like to roam the county, I'd still say Navigon. (They are the same price.)
In my mind, there are only two real turn-by-turn apps for the iPhone. It's a Navigon and Tom Tom game. They both are from great companies and offer comparable services.
The best suggestion I can offer is the following:
Get a car mount! The iPhone needs to be close (attached) to the windshield. The GPS transmitter in the phone isn't the best to acquire a signal when on a seat. I have
this one.
Next, get some type of charger + Audio output.
I use
this charger and
this for audio.
Audio is important because -- well -- you need to hear directions and your music. (Navigon handles driving directions with music well. It's lowers the music volume and speaks.)
Any GPS app will murder your battery. If you plan to use the app for more than 15 minutes, it'll need to be plugged in. Don't spend a lot of money on either the charger or tape/FM. It's just not really worth it.