One potential way to look at this book is to trace how Sal Paradise, the protagonist, changes throughout the book in response to his friendship with Dean Moriarty. You could make a chronology (or, if it helps you, a map) of his travels with Dean and show how he changes. At first, he is enthralled by Dean and his adventures and his relationships with women. However, when Dean and Sal are in Mexico, Sal starts to sour toward Dean, particularly when Dean leaves him when Sal is very sick. What kinds of realizations does Sal have about Dean in this moment? How does Sal change when he returns to New York and truly falls in love with Laura?
Your thesis statement could be an overall statement about how Sal changes in relation to his feelings about Dean over the course of the entire book. Your thesis could contrast how Sal feels at the beginning of the book towards Dean with how he feels at the end. This is only one idea; the idea is to step back and look at the overall themes and characters in the book and then to produce a statement that is reflected in the text.