Recent irradiation experiments have shown that smaller vacancy clusters are observed in Ni80Pd20 compared to Ni80Fe20. Using atomistic calculations, we find that the vacancy energetics are significantly different between the two alloys. Ni80Pd20 has lower vacancy migration barriers and lower vacancy-vacancy binding energies than Ni80Fe20. The consequence of these energetic differences is observed in molecular dynamics (MD) simulations, where despite higher vacancy diffusivity that would help in cluster formation, significantly reduced vacancy clusters are observed in Ni80Pd20 than Ni80Fe20. Calculations show that binding energy decreases and formation energy increases with increasing Ni-Ni bond lengths, and larger Ni-Ni bond lengths are observed in Ni80Pd20 than Ni80Fe20. Thus, the reduced vacancy-vacancy binding and higher formation energy due to longer Ni-Ni bonds in Ni80Pd20 are possibly the underlying reasons for smaller vacancy clusters in Ni80-Pd20 than Ni80Fe20. This study illustrates the unique effects of alloying elements on defect energetics and microstructural evolution in random alloys.