South Africa is large and varied enough that you could spend a month and still feel you've missed half of it. These are the experiences that most justify the journey.
Kruger National Park
One of Africa's great wildlife reserves, Kruger is home to the Big Five (lion, leopard, elephant, rhino, buffalo) and hundreds of other species across an area the size of Wales. You can self-drive — no guide required — on good tarred roads between well-equipped rest camps. The experience of watching a lion cross the road twenty metres from your hire car is one that doesn't fade. See Kruger National Park.
Cape Town and Table Mountain
Cape Town sits below one of the world's great natural landmarks. The cable car to the top of Table Mountain takes seven minutes; hiking the Platteklip Gorge trail takes about two hours and is worth it. Beyond the mountain: the Cape Peninsula, Boulders Beach penguins, the V&A Waterfront, Robben Island (where Mandela was imprisoned for 18 years), and the beautifully preserved Cape Malay quarter of Bo-Kaap.
The Garden Route
The coastal strip between Mossel Bay and Storms River is South Africa's most scenic road journey. Dense indigenous forest, sea cliffs, lakes, and small harbour towns follow each other in quick succession. Knysna's lagoon, the Tsitsikamma National Park, and the Cango Caves near Oudtshoorn are highlights along the way. See Garden Route.
The Winelands
Within an hour of Cape Town, the valleys of Stellenbosch, Franschhoek, and Paarl are lined with Cape Dutch estates producing excellent wine and some of the country's best food. Franschhoek in particular has become a serious culinary destination. See Winelands.
The Drakensberg
The "Barrier of Spears" — the great escarpment that defines the eastern edge of the interior plateau — rises to over 3,000 metres and forms one of southern Africa's most dramatic landscapes. The Cathedral Peak area and the Royal Natal National Park offer spectacular day walks and multi-day trails, along with San (Bushmen) rock art sites that date back thousands of years. See Drakensberg.
Soweto
The largest township in South Africa is not a museum, it's a city — about 1.3 million people, Orlando Towers, Vilakazi Street (the only street in the world that housed two Nobel Peace Prize winners: Mandela and Tutu), and excellent food. A guided tour from Johannesburg takes half a day and is one of the most genuinely illuminating things you can do in South Africa. See Soweto.
The Whale Coast and Hermanus
From June to November, southern right whales come to calve in the waters off the Western Cape. Hermanus offers some of the world's best land-based whale watching — you can watch from the cliff paths without a boat ticket. The old town is pleasant, and the drive from Cape Town along the coastal road through the Overberg is lovely.
Addo Elephant Park
If Kruger feels too far, Addo near Port Elizabeth offers Big Five game viewing at a fraction of the cost and crowd levels. It's the anchor for the Eastern Cape's developing game corridor.