I think it will be Natsu and Zeref vs Acnologia, Natsu vowed to kill Acnologia and the author often redeems characters, and a major point in the series has always been sibling bonds.
I think that will be the final fight in the series.
The story may be all about friendship, but Natsu shares Makarov's belief that blood ties don't matter if those who are related to you would harm the people you care for. Zeref may be Natsu's brother, and the reason that Natsu is still alive in the present day, but considering all of the suffering that he and his followers are responsible for, I highly doubt that Natsu would fight alongside Zeref.
As such, I think it would be most appropriate if the dragon slayers, with the help of their exceeds, killed Acnologia (since he is responsible for the deaths of all the dragons who raised the 1st and 3rd gen slayers) and Natsu killed Zeref sometime afterwards (with END being released at some point during their fight). Since Zeref is the main antagonist, it would make sense for him to die last.
