When I look at the opening explorers, the moves seem to be arranged based on how often they are played. Just because they are the most popular, should I assume they are also the best moves to play?

For example, in chessgames.com, the most popular Black response to e4 is c5. The 2nd most popular response is e5 and the 3rd most popular one is e6. If I were playing Black and White played e4, is there any good reason to play e5 or e6 instead of c5?