Very, very easy to drive over there!
All their road signs go by the compass... so make sure you know your East and West's!!! Never really needed a GPS system.. and have driven from Canada to Key West without any problems.
The only things you have to watch out for.. is the inside lanes sometimes disappear without warning, but in the US you can 'sit' in any lane, so try sticking to the middle lane on the Interstates. Also watch out for the road signs, they usually come up 'well before' the actual exit.
A good point, is that you can turn right on any road, unless it states 'no right turn' (usually at traffic lights) - I wish we had this rule over here.. how sensible.
When you come to a junction (stop sign), everyone goes 'in turn' ie. if you come up to a junction first, you move off first, and so on.
The general pace of driving over there is much slower.. so just 'relax' and take it easy!!