1) E.N.D. stands for Evil Natsu Dragneel.
2) Zeref said himself that Natsu is the only person who can beat him (in the Tenrou arc). Later in the manga, (Tartaros arc), Zeref said that either Natsu or E.N.D. can beat him. Suspicious, huh? Yeah. It is revealed that Igneel could not defeat E.N.D. suggesting that when he met Natsu, he tried to kill him, but failed, because he loved Natsu and got too attached.
3) Another thing is that in the Tenrou arc, Zeref knew who Natsu was, and Zeref created E.N.D., so of course he would know who Natsu is!
4) Zeref tells Natsu to choose between life and death. He's practically telling him that he'll have to decide if he wants to live or kill himself for everyone else's sakes. We all know that when Natsu realizes that he's E.N.D. he'll want to die instead of hurting his friends.
7) Jackal couldn't believe that Natsu was human... I smell something fishy here. And in the manga, it says that Natsu's power is on par with a demon! Or maybe he is one...
10) In Edolas, Natsu called himself the Great Demon Lord Dragneel. Great Demon Lord. Demon Lord. Demon. Think, why would Mashima do this? Maybe to convey that Natsu is a demon, and "lord" can represent how he's the strongest of all demons.