There are many ways to answer this Q, depending upon what you like to do and want to get out of the trip.
Many travel to South Africa as part of an African roots experience, which might also include visits to other sights in West Africa. Others travel for the natural beauty of the place and for its wildlife. Yet others seek cultural and historical perspectives from a land that has recently abolished apartheid.
So, I don't know what you seek; but, I will answer this giving you a blend of options.
1. Capetown/Table Mountain/the Winelands
"The natural beauty of Cape Town makes it one of the most attractive cities in the world. Cape Town boasts beautiful beaches as well as the impressive Table Mountain right in the heart of the city. The restaurants are world class, and so are the wines. Cape Town is also one of the most culturally diverse cities in Africa and has reputation for social tolerance."
"The Winelands are situated east of Cape Town among beautiful mountains creating some stunning vistas. The region is steeped in culture and history with some excellent examples of typical Dutch architecture dating back to the 17th century. The Winelands encompass several regions each with their own wine tasting tours."
2. Kruger National Park
"Kruger National Park is Africa's oldest established wildlife park (1898) and offers one of the best safari experiences in Africa. It's situated north of Johannesburg and takes about 5 hours to get to by car. It boasts the highest variety of wildlife in Africa which includes the "Big Five" [lions, leopards, rhinos, elephants, cape buffalo], hippos, crocodiles, giraffe, cheetah and much more. Kruger is also one of the best maintained parks in Africa. The roads are all good quality and there's no need to rent a 4x4 vehicle."
3. Soweto
"Soweto may not be the most beautiful place you visit in South Africa, but it certainly ranks among one of the most important and interesting sights in the country. Soweto is a sprawling township situated just outside of Johannesburg and over 3.5 million people call it home. Much of the struggle against Apartheid played out in the slums of Soweto, and the township was in a virtual state of war during the 1970's and 80's. Nowadays, Soweto is a mixture of rich suburbs and poor shanty dwellings where crime is rife. But Soweto is also home to some of the most vibrant music and theatre South Africa has to offer.
When you visit Soweto it's certainly worth taking a tour. Not just because it may be the safest way to see the township, but because the history of Soweto is what makes it so interesting. Soweto also covers a huge swath of land, over 90 square miles, so it's easy to get lost."
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Many who travel to South Africa and who are interested in nature, make a special trip north to Botswana and Victoria Falls. Victoria Falls is located where Botswana, Zambia, and Zimbabwe meet. I didn't include this in my top 3, as this is not in South Africa. But, depending upon how frequently you plan to make the trip to this part of Africa, you may find it rewarding to add a couple days to your trip and take a flight and tour of Victoria Falls. I refer you to the Frommer's link below if you are interested.