I'm not really an e4 player, but I throw it out there every once in a while to keep my regular opponents guessing. With that in mind I must say I find the Sicilian to be the easiest main e4 defense to play against. Black is simply unable to centeralize his pieces, so if white just centeralizes his pieces and then proceeds to open the center he seems to have the better game.
really i thought sicilian was most difficult to play against. I thought French was the most easy . Not to play good against but to play against, in sicilian you need a lot of knowledge to not lose really really fast.
jhni