Most, if not all, hire cars are automatic so you don't have to change gear, so you can concentrate on the driving. The parking brake is often a foot pedal under the dashboard (and it may have a release lever in the footwell) rather than a hand brake. So familiarise yourself with the car controls before you leave the airport. The rental company should also provide a basic driving map showing the major routes and attractions, we will also provide driving directions showing our suggested route from your arrival airport.
Most of the driving laws are similar to the UK except that you are on the other side (I say the wrong side!) of the car and roads. There are a couple of major exceptions, you can turn right at a red traffic light at most junctions (a sign will tell you if you cannot) - but only if you stop to check it is clear and safe to do so. There are no roundabouts to confuse you.
If a yellow school bus stops you cannot overtake it, even coming the other way you have to stop at a working stationary school bus.

Parking isn't usually a problem as America is car orientated so you'll find parking spaces everywhere. The individual spaces are normally much larger than those we are used to in the UK and the car parks, especially at the theme parks are huge, so make a note of where you park the car. We have been told by several guests that they have had to embarrassingly ask park security to help them find their cars!
Remember - Parked cars will get very hot inside so be careful where you leave your cameras, lunch, drinks or children, they may be ruined when you return! And do not leave any valuables on display in the car.