South Africa is a big country with numerous sights one might want to see during one holiday. In order to do that, plan at least a three weeks trip and still you will not be able to see all the country has to offer.
Essential destinations in South Africa are the Kruger National Park, the Garden Route and Cape Town. Ideally to get around quickly are flight transfers and there are reasonably priced flights available to connect Cape Town with Kruger and further to Port Elizabeth for the Garden Route. Using all flights it is possible to see even more regions of the country. However, many people love to do self-drive to explore South Africa their own way. Three weeks will be sufficient to drive from Johannesburg to Kruger for the African safari experience, then down through Swaziland to the Indian Ocean coast of Kwazulu Natal for beach, watersports and safaris and with a short flight from Durban to Port Elizabeth to carry on either in the Eastern Cape with more safaris or to continue directly to the Garden Route and further to Cape Town, maybe with a short visit to the Karoo in between. That sounds a lot? Yes, it is, but it is possible and all places are wonderful.
It makes sense to plan a round trip through South Africa in a flow. It is not working to plan driving Kruger, then Kwazulu Natal and then Transfrontier Park. The distances are huge and there are not everywhere good roads for fast driving. Driving at night is not an option and driving times need to be planned carefully. In some areas like Kruger Park the GPS will do funny things. Have a map and get directions to lodges, rather than relying on electronic devises. For the main roads GPS is fine or even Google maps, but the dirt roads in the bush will not work with that.
Plan rather longer stays of a minimum of 3 days than being constantly on the move. The driving is tiring and it is just nice to be able to really unpack and rest for a while. Rather choose a home base in a region from where you explore what you want to see. And also here, be aware of the distances and that they are measured in hours, not in kilometers in Africa. Planning your South Africa round trip carefully will make sure you have a wonderful holiday with amazing wildlife sightings and fantastic landscapes.