MAGUIRE: You're just a kid. You don't have the faintest idea what you're talking about.
Maguire knows that Will is smart, so smart that it takes him (Will) less than a minute to find Maguire's biggest vulnerability—his dead wife—and start pressing on it. But even though this get to Maguire at first, Maguire presses back and reminds Will that being smart doesn't mean that he's lived a full life. And that's the kind of thing Maguire wants to help him with.
MAGUIRE: So, if I asked you about art, you'd probably give me the skinny on every art book ever written. Michelangelo.
Maguire knows that Will has lived his entire life through books. But reading books is not the same thing as experiencing life firsthand. One of Will's biggest problems is that he's scared to experience things firsthand. In books, he can control everything. But in real life, there's a lot of uncertainty and Will finds this really scary.
MAGUIRE: But I bet you can't tell me what it smells like in the Sistine Chapel. You've never actually stood there and looked up at that beautiful ceiling.
Once again, Maguire brings up an example of something he's experienced firsthand that Will hasn't. Of course, he's not saying he's better than Will because he's traveled. His point is that he's willing to go out and experience things, while Will is only comfortable in situations he controls completely. This is a comfort zone that Maguire will try to get him out of.
MAGUIRE: You're a tough kid. I ask you about war, you'd probably uh... throw Shakespeare at me, right?
As his speech continues, Maguire keeps listing all of the things that Will has only experienced through books. His basic point is that there's a whole lot of stuff in life that you can't learn from books. There's a lot that you can only learn firsthand, and this is the stuff that Will needs to go out and expose himself to.
MAGUIRE: I look at you: I don't see an intelligent, confident man. I see a cocky, scared s***less kid.
Finally, Maguire tells Will what he really thinks of him. Will thinks everyone sees him as a genius, but Maguire only sees a cocky scaredy-cat. He never argues for a second that Will isn't a genius because it's clear that he is. But he wants Will to put more focus on the stuff he doesn't know.
MAGUIRE: You're an orphan, right? Do you think I'd know the first thing about how hard your life has been, how you feel, who you are because I read Oliver Twist?
To help Will see his point, Maguire turns the tables on him and asks how he would feel if Maguire pretended to know about his experience as an orphan just from reading Oliver Twist. This point seems to hit home with Will, and in a way, it marks the beginning of his real growth into adulthood.
MAGUIRE: I can't learn anything from you I can't read in some f***in' book. Unless you wanna talk about you, who you are. And I'm fascinated. I'm in. But you don't wanna do that, do you, sport? You're terrified of what you might say.
Maguire knows that he'll never have a real conversation with Will unless Will learns to open up and talk about himself. So he tries to remind Will that the only stuff he can say that's actually interesting is stuff about himself. After all, Maguire can go to a library if he wants to hear someone quoting everything he says from books.
WILL: Well, I think that's a super philosophy, Sean. I mean that way you could actually go through the rest of your life without ever really knowing anybody.
Will turns the tables on Maguire when he catches Maguire retreating from life because of his wife's death. He mirrors Maguire's own words back to him and basically calls him a hypocrite for not following his own advice. This is a big moment in the movie, because this is when both Maguire and Will start growing as a pair instead of as individuals.
WILL: So I was… I was wonderin' if uh... if, you know, you'd give me another crack at it, you know, lemme take you out again.
Will takes a big step in growing up when he goes back to Skylar after blowing her off and asks her for a second date. Normally, he would retreat from someone he feels such strong feelings for. But after talking to Maguire, Will knows that he needs to start taking more risks with his heart if he's ever going to grow as a person.
MAGUIRE: Hey, Will? I don't know a lot. But you see this? All this s***. It's not your fault.
In the movie's climax, Maguire confronts Will with photos of the injuries he got as a foster child. Will tries to brush the injuries off as unimportant, but Maguire tells him, "It's not your fault" and keeps repeating this phrase until Will breaks down and cries. We can tell that this is a real moment of healing because it's the first time Will has really broken down and been vulnerable in front of another person.