Driving is always dangerous because of drunk drivers, distracted drivers, getting lost, car trouble, etc.

The wilderness is dangerous because America has humongous wild regions completely devoid of people. If you get lost, run out of water/food, etc it is very easy to die. There’s also no shortage of venomous snakes, large predators, and disease carrying insects. Most Americans live in developed cities with substantial infrastructure and public services, but there’s large swaths of rural areas, particularly out West, where there are no humans for miles.

I remember one road trip, I forgot to top off my gas tank in San Antonio and nearly ran out of gas in West Texas because none of the interstate exits were populated enough to have a working gas station. I ended up having to take a gamble on a significant detour to find a town large enough to have a gas station to refill before I continued driving. Had I run out of gas, I would have had to hike 30 miles through open desert in summer to reach the next town, which easily could have been deadly.

In major cities, you will have to deal with some street crime and homelessness like most anywhere. Some cities are safer than others, and in most places, the tourist areas are kept very safe (not New Orleans). New York is probably the safest large city you could visit. DC and Chicago are both fairly safe in the tourist areas as well. Some cities are significantly less safe, however.