Zeref: immortal because cursed to live forever. How can you even defeat an immortal being?
There's probably something about the curse… Zere created the demons of Tartaros with curses too, and just like any magic, any curse should have a weak point.
Maybe we'll eventually see Ankhseram if he ever believes that Zeref has learnt his lesson and understood why it's not good to play with life and death.
Maybe the FT guild can use the same seal that Mavis used on herself so that Zeref is sealed away.
But again, Zeref created END so that someone could defeat him, so maybe dragon slayer magic can affect him somehow… and Natsu will beat him before they seal him or something.
Acnologia: he's way too overpowered… if Fairy Sphere gathers an equivalent amount of magic to protect against an attack, then it means that it took 7 years worth of magic from the best members of Fairy Tail to counter a single attack from Acnologia… Ok, now they are stronger, so maybe it would be less >_> Still, it's just one attack… and all the dragon slayers were powerless against dragons during the GMG.
They might need all of the dragon slayers, Natsu as a demon already, and… Zeref?
It's still a bit too messy in my head for me to make any real theory though…