The distance between O'Hare and downtown has been mentioned. You will need to leave plenty of time for travel between destination and terminal. Predicting travel times in this city is risky business if you're running late.
But there are plenty of other issues to occupy the focus of O'Hare travelers.
Overbooking is a common practice in this busy hub airport, and you'll have an opportunity for free future travel if you wish to be bumped. But if you would rather not take a later flight, realize that it might happen to you involuntarily.
Walking distances at O'Hare can be longer than expected for some travelers, especially when moving between the three terminals.
Another issue: much like other major hubs, on-time records here are fairly dismal. The potential for disruptive delays should be considered.
Alernative airports include Midway on the south side of Chicago and Milwaukee's General Mitchell Int'l Airport.