Plot/Story
Pretty much, Sena Kobayakawa is a very wimpy kid who has been bullied his whole life, except when he's being protected by his childhood friend Mamori. However, being forced to do errands for people have given him amazingly fast legs, which does not go unnoticed by the American football team captain, Hiruma, who forces him into the American football club. Sena, reluctantly at first, becomes the ace of his team when he saves the team from defeat in a tournament. Hiruma, not wanting to reveal his identity to other teams, gives him an eyeshield to cover his face and gives him the nickname "Eyeshield 21". Soon, others join the team, all with the common goal to reach the top.

The story is pretty similar to other sports stories in some ways, like the way it's a bit unrealistic, and they regularly compete with other teams, growing stronger as they climb up to the top, which might make the story a bit linear. However, the backstories behind the many players are really well made, and really make the plot a lot more interesting. There are some really great and unexpected plot twists as well. The author is also very good at explaining the rules of American football to readers that have no idea how to play, though it is a little simplified compared to real live football.
Characters
Arguably the best part of the manga, every character is unique and different, and the character development is very good as well.
Sena: He's a wimpy kid that used to get bullied a lot, but all the running around doing errands has given amazing legs, giving him an untouchable speed. He originally signed on the football club as the team secretary, but he is forced by Hiruma into becoming their ace running back, Eyeshield 21.
Hiruma: The captain of the American football team, and he is EVIL. He's very trigger-happy as well, and provides a lot of the humor in the story.However, he is also the quarterback, and is probably the smartest person on the team, making him essential during games.
Kurita: A very cheerful and fat guy who plays as a lineman. He's quite huge, which makes him look quite comical, but his power is nothing to be laughed at. He tends to be pretty emotional, though, and isn't exactly the brightest person around.
Monta: He was originally trying out for the baseball team, but because the only thing he could do was catch, he didn't make the cut. He is recruited onto the football team, though, and becomes their receiver.
Shin: Considered the best linebacker in Japan, he becomes Sena's biggest rival. He's ridiculously strong, can run at nearly the same speed as Sena, but is very, very bad with electronics.
There is quite a big cast in the story, so I'll just stop here so as not to spoil anything.
Drawing Style
Eyeshield 21 is a very well drawn manga, and it fits the manga very well. Of course, it's not so amazing that you'll read it just for the art, but it's still good artwork.
Enjoyment
This manga gives a lot of enjoyment. It's a very funny read, and is helped a lot by the crazy cast of characters. The matches are very exciting though, and will definitely keep you on edge during the later matches.
Overall
Eyeshield 21 is a very good read, and you should definitely at least try it out. Of course, if you really despise sports manga, this might not be the manga for you, but I'd suggest you try it anyways.