"With university lecture halls rivaling small-concert venues in terms of the number of those in attendance, it is incumbent upon incoming freshmen--most long coddled in an intimate learning environment--to become adept at navigating the treacherous waters of anonymity."
The opening modifier tells us that a university lecture hall may hold as many students as a small concert hall. In other words, some university classes have a whole lot of students!
"It is incumbent upon" someone means that it is something one must do. Who are we talking about? Incoming freshmen, who the author believes have been coddled (spoiled or indulged) in smaller settings, presumably in high school. What must these freshmen do? They must learn to "navigate the waters"; in other words, they must learn to deal with something effectively. What do they need to deal with? Anonymity--being part of a crowd in which you are not well known, or perhaps not known at all.
So the author is saying that high schoolers are coming from smaller, more intimate learning environments into these huge college lectures. They're used to having a teacher who knows their name and perhaps knows their family, who notices when they are late or are having a bad day or are not working up their potential. They have to learn how to function effectively in an environment in which they are not well-known and in which the professor may not even be aware of their presence.
I hope that helps!