Movies that would have been huge hits if the lead had been

I'm not sure if I agree with your premise although it's possible. There is movie called Set It Off which has four female back leads and it was a critical and a commercial hit. It was New Line Cinema biggest success of 1996. Also a pretty good movie. 

Sigourney Weaver and Holly Hunter were pretty good as the leads in that movie and I'm not entirely sure if Aliens would've been a bigger hit if it had other lead other than Sigourney Weaver.