The small planes have roughly the same fuel consumption per passenger per mile as the large ones these days (AIUI the disadvantage of more engines balances the advantage of a larger plane. Maybe a hypothetical "twin-engine A380" could be more fuel-efficient - I'm not sure why that hasn't been attempted). So assuming equal loadings on all flights, point-to-point would be more fuel-efficient than a hub model (since passengers travel further in the hub model). Obviously if point-to-point leads to planes flying half-empty then at some point that becomes a bigger effect.
To add to this analysis: the hub model, by definition, add at least one, and possibly two flights. It's not just an increase in distant, but all the fuel inefficiency of starting, landing, idling on the ground etc.
An A380 has about 1,400 kN available from its four engines. A twin engine A380 would need two engines developing at least 650-700 kN just to get off the ground. For reference, the GE9X being developed for the 777X develops 470 kN.
To make things more complex, there are regulations that require an aircraft to be able to continue takeoff should one engine fail. To match the thrust available of an A380 on 3 engines would require nearly 1000 kN of thrust from a single engine, way beyond current commercial jet engine technology.
Rolls Royce had to design special extra large engines for the A380. Because of the large diameter of the fan they had to use clever blade geometry to overcome problems with supersonic airflow at the ends of the fan blades. So I'm guessing that two even larger engines would be tricky.
A380's engines are the same size as the early-90s 777 engines, and smaller than both the GE90 and the new GE9X. They didn't have to do anything tricky for them.
You may be thinking of the new Pratt & Whitney PW1000G, which will be on the A320neo, which has a geared turbofan for that reason.
