I spent 2 weeks in South Africa last August and will definitely go back. We travelled the Garden Route from Port Elizabeth to Cape Town. We had a couple of days on safari in the Addo Elephant Park near PE, which was good, but you're never going to see the Big 5there, so if game viewing is your thing head further north (Kruger NP).
If you're into whales, sharks, stunning scenery etc. the southern coast is the place to go. I recommend Plettenberg Bay and Hermanus for whale watching (has to be June-Nov though). Cape Penninsula and Table Mountain are great for scenery. We found that 2-3 days in Cape Town was plenty (and 1 day in PE - nothing much there).
It's a fascinating country, although the legacy of apartheid is still very much there (there are squalid townships around most towns). Everyone we met was really welcoming, without exception.