Not close to booking air yet, but tickets from Chicago to Capetown (2 stops) and Johannesburg to Capetown are $1530pp on Vayama...this is way lower than the $2000+ I see everywhere else.
Flights are on Lufthansa and South African Air, so definitely reputable airlines.
Vayama isn't much different from Orbitz or Cheaptickets. Usually the prices are the same, but I have found a few times when Vayama comes up with a less expensive price, and I've booked with them in those cases. The experience was pretty much the same as booking with one of the other similar websites.