They are different. In opening, sometimes you have to play exact moves if you are facing a certain line. I have a line where I can click out 18 moves and get a great potion, a couple times against GMs on icc, but that is rare. most of the time you hope to get a comfortable position out of the opening, so a general knowledge of openings are required.
Middle game you are much more likely to use your judgement and calculating abilities, where there usually are several ways to play the potion at any given moment.
Question for 1800+ players:
Is it more difficult to play the opening or the middle game?