Long distances is all relative, I guess, the longest section you have is Knysna - CPT which is probably around 6-7 hours including stops.
Oudtshoorn is between Knysna and Cape Town though, so you may want to reconsider the order you do things.

Personally I would drive one way, and fly back the other, especially on a relatively short trip such as yours, I would spend 4-5 days in CPT, and 1 or 2 nights in the other places you mentioned.

You didn't say what you would like to see or do, so it's hard to say which of those places are "better".