To discuss the "setting" of On the Road is interesting and informative about just what’s going on in this text. Sal is restlessness, right? He keeps needing to move, to go somewhere else – but we really only see him in four major American cities – New York, Chicago, Denver, and San Francisco – each of which takes on a persona and describes a particular phase on Sal’s travels.
The temporal setting is a post World War II America, a time that Sal and his friends find full of intellectual falsity (read: the arty types "sucking up the blood of America") and in fact rather aimless. There is a need to go, to be, to do something, but this Beat Generation, defined by its time and circumstance (i.e., the setting), doesn’t know where or how to channel that energy.