We rented a car for 9 days in South Africa, and driving ourselves around worked pretty smoothly. The main roads are very good, with mostly clear signs. There's a good expressway toll road between Johannesburg and the Kruger area. The tolls come out to about $3 to $4 for an hour's driving.
We picked up our car from Europcar at the Johannesburg airport. We paid about $34/day for a Toyota Corolla, including coverage, taxes, etc. That seemed to be a pretty standard rate for that size car (manual) at various places on the Internet, although you can easily pay more if you just go straight to someplace like Hertz. With a rental car, you can also get a "free" rental cell phone from the airport. Not quite free in that you have to pay 10 rand(about $1.50)/day in insurance, and, of course, you pay for the calls you make (reasonable charges). That worked well for us.
Most drivers are pretty courteous outside of the Johannesburg-Pretoria congestion, for example, pulling way to the right to let you pass on a narrow road. But the Johannesburg area has very bad traffic jams at rush hour, just as bad as those in any American city, such as my home area of Chicago. We were coming into Johannesburg on a Friday afternoon, and the outbound lanes of the expressways were totally jammed, turned into a parking lot. (Coming against the main flow of traffic, it wasn't bad at all, though.) So definitely do not plan to drive around Johannesburg at rush hours. The freeways around Jo'burg (and elsewhere) have a 120 kph limit when they aren't jammed up, and on Saturday, it was no problem going that fast (people in Chicago drive just as fast on the freeway, but the limit is only 55mph/80kpm).
Thankfully, we didn't have any problems with safety. Car-jacking is a problem in South Africa, apparently, and we even saw a few signs at selected points on the highway saying "Hijack Hot Spot", which is a little scary. So pay attention to safety warnings you can read elsewhere. We tried to avoid all driving at night, both in cities and out.
There are "squeegee guys" at some stoplights in Jo'burg, just like you'd find in American cities, offering to wash your windshield for tips. It wasn't a big deal when one cleaned ours before we waved him off and we paid a couple rand, but with all the safety warnings and the city's reputation for crime, it is a little uncomfortable.
There are plenty of gasoline (petrol) stations, and the price of gas was just a little bit higher than in the US, not a budget breaker. Gas stations are still full service, and they take cash, not credit cards. We saw ATM machines at some of them. They are also a good place to stop to ask directions after your tank is filled.
Since I'm from America, I had to adjust to driving on the wrong side of the road. You do get used to it pretty quickly, but it is worthwhile to have someone remind you out loud "stay left" when starting out or occasionally. (I never did get used to the turn signal being on the right of the steering column and probably inadvertently turned on my windshield wipers 50 times.)
Having our own car certainly gave us the freedom to explore wherever we wanted to, and with four people, it was an economical way of touring around. We didn't have 4WD and didn't really need it, even in Kruger or game parks in Swaziland.