This is ultimately the equation. There are not very many routes that you can fill up an A380 on without cutting ticket prices enough to get people to change their schedule. Add to that:

1. It takes a long time to load that many people, so it only makes sense on long routes.

2. You need special facilities at the airport: bigger taxiways, special gates, large waiting areas, extra customs officials. This cuts into the profits.

3. Since there are so few routes, you won't have many 380s, but you still need a set of pilots trained on them, plus a reserve in case people get sick, can't make it to the airport, etc. That reserve crew isn't shared with your other smaller aircraft, so it's an additional expense. The same thing goes for maintenance.

4. Much of the theoretical fuel and maintenance economies of scale you get from flying a larger aircraft are lost with four engines instead of two.

On point 4: four engines have some disadvantages, but in terms of fuel consumption the difference is within 1% or 2% of two engines. The issue has more to do with maintenance, and reliability: with two extra engines, you are that much more likely to have one going tech and be grounded.

EDIT: interesting link, that contradicts some of what I say above: https://leehamnews.com/2015/12/11/bjorns-corner-twins-or-qua...

Also, aircraft are certified to be able to complete take-off with one engine failure.

Thus, twin engines have to have basically 100% reserve, while the 4 engines only need to have 33% reserve (to make up for one engine failing).

Norwegian currently have a 787 stuck in Iran with a broken engine, so I'm not sure they can take off with only one engine

From what I gather, certification requires that they can take off successfully if an engine fails during the take-off run (after V1). I doubt that they're allowed to leave with half the engines inoperational already.

With you… like this Thomson plane that had a failure due to bird ingestion during take off at Manchester - https://www.youtube.com/watch?v=9KhZwsYtNDE

For point 3. I believe Airbus has a lot of commonality between its cockpits on different aircraft, so it is easier to get type certified on an A350 or A320 if the pilot already has a rating on the A380. This means the reserve crew can fly the other smaller planes when not required for the A380. Boeing has not had this commonality until recently - I think it was a selling point for the 787 that it had the same cockpit layout as the 777, thus minimising crew training.

And then there's the airport gate retrofit cost that the A380 has. The 777X has a clever solution to that (folding wing tipes), but it's still smaller in capacity.