Yes there are many differences - airspace for one - as well as differences in the rules - VFR cruising altitudes as an example. However, flying is easier in the USA from weather briefing, notam briefing, to airspace transits. RT is easy, the format is the same as everywhere else - who you are, where you are and what you want. You just need to know what you want!
As suggested get a copy of the FAR/AIM 2009 and gen up on it (it is also online somewhere). It contains all the relevent information and the stuff you will need to know.