When your play in an opening variation becomes mechanical, then it is time to play something else.
How to know when to add to your repertoire ?
Modern masters prefer the last one, since they want a small edge with white. An extremely sharp game is hardly the way to keep an edge (since a small inaccuary loose the game or the edge), and in d4 you can make a few mistakes and still be in the game.
I believe the real reason that d4 outshines e4 these days is that it is easier for black to play for a draw after 1. e4. This is also why, although e4 still appears at top level tournaments where players playing black may still be looking for a win, it has completely disappeared from the last 3 WC matches where a draw with black is considered a good result. The only time Anand played 1. e4 against Kramnik in their match was when Kramnik had to win to stay in the match.
Note: It was Kramnik who basically killed 1. e4 in matchplay by drawing every game with black in his match against Kasparov.
Theres really only two 'drawing lines' against 1.e4 that have appeared in WC matches..the infamous Berlin Wall and the Petroff. Its not Kramnik's fault that nobody has yet found serious winning chances for White in the Berlin endgame or that the White players have been scared to play the sharpest lines against the Petroff.
I pretty much just pick an opening and run with it - now unlike some, I HATE e4/e5 games as black, so I play the French and the Sicilian - but God knows I don't memorize hundreds of moves or lines. Just use the ideas, mostly. With white I almost always play e4 because I like the Ruy and the Sicilian from white's side.