First a caveat, I don't drive !!!
But my husband does, and we hire a car every time we come, also from the UK. Every car we have had comes with a sat nav, which we tend to rely on, except when it comes to the exits to Disney when we sometimes take a different one if we know where we're heading.
Just check which direction you should be heading along the major roads before you set off. Some signs will just say "I 4 west (Tampa)" for example. Helps to know whether you need to be going east or west.
Once on Disney Property the roads can be confusing, with several lanes and lots of signs. The sat nav is just as useful here.
Be aware that sometimes the sat nav will give you a toll route when you don't need to. However unless you are sure of an alternative route it's often easier just to go with it. More likely if heading to Kennedy or the shopping malls than Disney / Universal.
Hubby tries to stay in a middle lane on the main routes. Sometimes the right lane is a "must exit" lane, other times you get an exit like our motorways. If you try and stay in lane 2 then you can easily get into the exit lane if necessary but not be forced off.
The driving on the right thing is OK, once you're in traffic because everyone else is doing it and it's hard to go wrong. Major junctions where you have to turn left across traffic usually have lines painted on the road so you can follow them. Be aware of the turn right on a red light rule.
We have got lost a couple of times. Once we ended up in Celebration and couldn't find our way out! And last time we were headed to Universal, and as someone said above it had us going off the I4 early and we went right round the back. I think it had directed us to a trade entrance - probably didn't check which address we picked from the list.
If you have a retractable roof make sure you know how to get it up again, and if you can do this on the go. We saw a couple of cars once that had to stop to get the roof up, in the middle of a thunderstorm. They were drenched!