Yes, I have spent months travelling from Kenya down to South Africa and been to SA many times.
Adults can take Doxy rather than Larium, people we travelled with had hallucinations and all sorts from Larium, but Mosquitos were everywhere, there is no way you can try to avoid being bitten, even with Deet, garlic tablets, long legged pants and shirts and mosquito nets to sleep in.
In SA - Hluhluwe–Imfolozi is a great alternative to Kruger, less well known and not as busy. We self drove round it in a hire car.
Nowhere near as good in my opinion as the Serengeti or Masai Mara in Kenya/Tanzania, but if you're only going to SA those are good choices. We stayed near St Lucia in the coast too - beautiful beach.
Cape Town is lovely, has great beaches, you can go to Robbin Island, lots of wineries nearby and up Table Mountain.
I only felt unsafe in Jo'Burg, didn't feel unsafe down the coast at anytime, although I did get mugged and pickpocketed in Cape Town.