You pose an interesting question. As far as I know there are no flights from Maputo, Beira or Pemba to 'tana in Madagascar, which would require you to head to Johannesburg for the onward flight to Madagascar. This would cost you an entire prehaps even two as I don't think there is a decent connection requiering you to overnight in J'berg.

Certainly for it's unique floral kingdom and associated endemic wildlife Madagascar has some truly exquisite wildlife, however lacks the big game and predators that are synonymous with the African continent.

With that in mind I would encourage you to consider two options: East Africa safari finishing with a coastal stope either on the Kenyan or Tanzanian coast.

OR

A southern African Safari with a visit to the islands off the Mozambiquen coast. The Bazzaruto archipeligo can be reached via Vilanculos, which in turn has irregular flights from KMIA, which would make the Sabi Sands/Kruger your best safari option.

Interestingly if you were to opt for the Quirimbas archipeligo, these are probably best accessed from tanzania (Dar) as the flight schedule south bound is better than the four hour flights from J'Berg to Pemba.

Night liife: Challenging, but would urge you to visit Maputo, which is developing into a buzzing city with exceptional seafood restauarnts and side walk cafe's. There are regular flights to Pemba, Beir & Vilanculos out of Maputo.

I will not make suggestions on lodging as there are a variety of niches ilsand lodges and frankly I have no idea what your tastes and budgets require.