South Africa's road infrastructure is excellent, so driving is a viable option but it does need to be carefully planned. South Africa is a big country and many travel agents have made the mistake of booking visitors on a day trip which they think is a 3-hour drive from their previous night's accommodation only to find that it is, in fact, a drive of more than 12 hours.
This really has happened so do make sure you don't fall into the same trap. Also - even if you do leave sufficient time for a trip in the itinerary, check to see if the visitors are used to travelling long distances. If not, rather break the journey, as fatigue is a major contributing factor in motor vehicle accidents.
In South Africa we drive on the left-hand side of the road and rental cars are right-hand drive. Most rental cars are manual or floorshift so check to see if they want an automatic. These are a bit more expensive.
All distances and speed limits are given in kilometres. The speed limit is 120km/h on the open road, 100km/h on smaller roads and 80 or 60km/h in urban areas.
Be aware that the roads in some rural areas are not fenced so you could find dogs, chickens, sheep and even horses or cows on the road, so it may be dangerous to drive at night. All the major car rental agencies have offices at the airports and in the cities.
Warn visitors to the country that if they are caught committing a traffic offence, e.g., speeding, they may have to pay the fine before they continue, as their driver's licence will make it clear that they are not likely to be in South Africa to go through the usual, rather long-winded process of collecting fines.
For the adventurous, there are some fun options. Renting a motorcycle is one, as is renting a four wheel drive, mobile home, or open top roadster. It is, after all, a holiday.