Most players start out playing 1.e4 and at first almost everyone plays 1...e5 to counter. You may become great at whipping out your favorite Ruy Lopez, Evans Gambit, Giuoco Piano, King's Gambit, etc.; but then as you rise the ranks you'll be meeting a lot more 1...c5's.
Now I sometimes joke that when I play 1. e4 I am tempted to write down 1...c5 on my scoresheet: because it is that popular at master all the way up to super GM and world champion level. The most infuriating defense (at least for me) is the Sicilian Najdorf: 1. e4 c5 2. Nf3 d6 3. d4 cxd4 4. Nxd4 Nf6 5. Nc3 a6
At first, I welcomed all 1...c5's as I am a fairly skilled attacker. But as I improved, so did Sicilian Defenders. Those scintillating attacks became either "failed brilliancies" (leading to great endgames for Black) or scintillating attacks but instead they were Black mating my King! I have Najdorf games from the Super Tournament Wijk aan Zee 2011. Hopefully these games help you understand how much work has gone on in just this one variation. Below is quite extensive theory on the Najdorf and it's just a small tip of the iceberg!
Please feel free to comment on your favorite line for White or Black in the Sicilian Najdorf and I'll try to leave my opinion promptly. If you are to be a successful 1. e4 player, you better have a good line against the most popular defense 1...c5 and the Najdorf!