Nobody is flying a 747 from Denver to NYC and I think the crews on 747/A380 type planes flying long hauls are often four pilots that alternate between 2 in the cockpit and 2 resting.
With all that said, airline margins on routes with competition are generally small. If you buy an economy ticket on a popular route (something like New York to Chicago), and you buy it not too early and not too late, the airline is probably just about breaking even on flying you there. Where they will make money on that flight are premium cabins, checked baggage fees, and all the people who pay an annual fee for their United or American-branded credit card so that they can get some miles or get lounge access or get a free checked bag or get elite status and be eligible for upgrades.
Airlines now make a huge chunk of their money by selling miles to credit card companies. They make almost no profit at all from economy-class ticket sales.