Not that I want to scare anyone, but on two of our three trips to Orlando we've had bumps in the car. One of them was fairly serious - a car went into the back of us at a red light, in heavy rain, and smashed the rear of our people carrier bad enough that we couldn't open it again (we took it back to the airport to change it, but ended up keeping it when they didn't have any others with satnavs). The other driver, who I did feel sorry for, ended up getting a ticket, and a court date.
Then last year I scraped a white van at an intersection - completely my fault this time, but the van drove off, so there weren't any repercussions.
Despite that... I have absolutely no fear of driving again this year - and I say that as someone who was terrified before his first visit. As others have said after about 10 minutes you'll be fine. My problem is more that I'm driving a vehicle that's bigger than I'm used to, rather than the US road system per se.
Everything over there is bigger, and easier to use - the lanes are wider, the parking spaces are so much simpler to park in, and leaving the highways is less bother than it is over here. Make sure you get a satnav with your hire car, though, as it'll take the stress out of dealing with exits, and the like.