need to fly from:

Newark/NY to C.T.

C.T. to Jnb

JNB to Kruger NP
Kruger to JNB

JNB to Vic. Falls
Vic. Falls to JNB

JNB to Nairobi
Nairobi to Safari then back to Nairobi

Nairobi to Cairo (Do the Cruise etc.)

Cairo to Sicily

Sicily to Rome/Naples then to Newark/NY

a lot depends on when you are going. check out kayak.com or other sites with the dates you are looking for. some I've found are:
JNB-Kruger (MQP) are from $279-$345 pp/rt
JNB-Vic Falls (VFA) are from $507 pp/rt
I think most if not all flights do a stopover in JNB before heading on to Capetown.

amolinaro - that is the great thing about the internet, you can find this information yourself. And then modify or change it to fit what you need.
regards - tom

You won't be able to fly from NY to Capetown. All international flights from the US go through Johannesburg.

Another option would be to route via a European gateway into Capetown, bypassing JNB. I don't think it makes a big difference either way in overall time. Depends how you prefer to break up the flights. We're routing via AMS this Sep. It's less stops for us vs via JNB (if you count the DKR fuel stop).