Smaller long-range aircraft make it possible to operate so-called "long, thin" routes, e.g. nonstop service between two second-tier cities. AUS-LHR, for example, which BA is opening with a 787 next year; you'd never see that route served with a 747. As route maps shift to emphasize long, thin routes the case for the 747 diminishes, as fewer long-haul flyers have to shuttle to a major hub to catch one. (Pan Am's whole network was built to get most passengers to JFK to catch transatlantic 747s; in the 1960s and 1970s the idea of transatlantic nonstops departing from PIT, CVG, CLT, was unthinkable, mostly because such markets were too small to fill up a 747, DC-10, or L-1011. It wasn't until the 1980s that 767s, and soon other twinjets, were allowed on intercontinental long-hauls.)

There will always be a business case for VLAs to serve the world's top 20 air hubs, particularly as slots there grow more precious. It's just a narrower case than before, and the population of VLAs (747s and A380s) will continue to decline.