The activity fraction expanded ensemble (AFEE) simulation technique has been extended to predict the vapor-liquid coexistence behavior of binary mixtures of molecular fluids. The systems of molecular mixtures studied are thiophene-n-hexane (a mixture of an aromatic compound with a n-alkane) and methane-n-hexane (mixture of n-alkanes with significant difference in size). Comparison with results from the grand canonical transition matrix Monte Carlo method and experimental data available in the literature has also been provided. Further, we have investigated the computational efficiency of the AFEE technique at temperatures where both compounds exhibit subcritical behavior (thiophene-n-hexane at 338.15 K) and where one of the components shows supercritical behavior (methane-n-hexane at 373 K). Canonical Monte Carlo simulations are also performed to obtain the radial distribution functions which have been used to study the structure of the coexisting liquid phases to gain insights into the molecular origins of the observed macroscopic phase behavior. The results show that the use of the AFEE technique results in a significant decrease of computational time at both temperatures. However, at conditions where methane is supercritical, the AFEE simulation methodology is severely undermined by the deviation of the logarithm of the activity vs activity fraction curve from linear behavior as well as swapping of the liquid and vapor boxes due to reduced free energy barriers.