Would physics allow us to build a really big airplane, say 5x the size of a standard airliner?

Physics is not the issue. You can make a plane wider, longer or higher.

It wouldn’t sell. Airlines have realized that large planes are uneconomical because runways, engines, wings, loading, unloading and timing of flights make 400 to 500 passengers the upper limit for cost effectiveness.

The main issue is health and safety. One of the rules is that you have to be able to evacuate a plane in 90 seconds. These are tested with volunteers in test conditions. A wider plane has difficulty getting all the passengers to the edges of the plane to get them off. So not wider.

Making them higher means more exits and longer slides. So you can get them off. However most airports have bridges at one height only. How are you going to get passengers up 4 floors without a 5-storey bridge, and that means sorting out passengers into 5 floors in the Terminal, which requires a complete redesign of gates. Very expensive and thus you have an aircraft that can hardly fly anywhere! So not higher.

It may be that the forces on a very long plane would put too much stress on it.