The Continental hub at Denver has already been mentioned, but in its day, it was the largest station in the CO system. At its peak in the late 1980s, Continental was bigger than United at Stapleton International Airport. In 1986-1987, Continental acquired Frontier and doubled the size of its DEN operations, adding dozens of extra flights, twice as many gates, and even an additional maintenance hangar.
I flew through DEN in 1991 and 1993 and I remember a sea of gold tails everywhere. The hub started to come apart in 1993-1994 and was almost completely gone by the time DIA opened in 1995. Originally, Continental was to occupy ALL of DIA's Concourse A (which is now the home of the resurrected Frontier.) I'm willing to bet that Continental's abandonment of Denver was probably the largest hub pullout in U.S. aviation history (although Eastern in Atlanta might deserve that title.)
Dallas Love Field (and then DFW after it opened in 1974) was the home of Braniff International.
Before Deregulation in 1978, Cleveland-Hopkins was one of United's largest stations. They occupied almost all of the 'banjo' concourse now used by Continental. United flew DC10s and 747s from Cleveland to Los Angeles, San Francisco, Denver, New York, Boston, etc... it was a mid-continent transfer point, just like Chicago O'Hare. United also had a large presence in Pittsburgh and a decent-sized operation in Detroit.
TWA had an entire concourse to itself at Chicago O'Hare prior to 1978. They scaled back their Chicago ops in favor of St. Louis and Kansas City (but mostly STL) after deregulation. Delta also used to be pretty big at ORD, as did Northwest, which in the mid-1970s ran several DC-10s to and from MSP every day.
And of course, there was the Eastern ATL hub, which for many years was bigger than Delta's. When they went under in 1991, Delta gladly picked up the extra gates and passengers...