Is the twin vs quad engine industry preference really challenged?
Why would Airbus go to the effort of developing the A330 when they could offer the A340? Both have the same airframe and differ mainly in the number of engines. With ETOPS requirements at the time of development (when they were known as TA9 and TA11) being just 2 hours (ETOPS 180 operations were only begun in 1989), the only reason for developing the 4-engined variant was its capability of flying long overwater routes.

The time it takes to check an engine is the same regardless of size, so having only two of them saves time and money. In addition, the higher power reserves of a two-engined aircraft allow for higher climb speeds and enable it to reach the most efficient cruise altitude faster.

Today, most airliner engines are no longer owned by the airlines, but leased from the engine manufacturer. They offer a simple thrust per hour model where the airline knows exactly how much the engine will cost them over time, maintenance included. The only open issue is how long the airliner is grounded due to unforeseen maintenance, and with four engines per aircraft the number of unforeseen snafus is twice that of a twin.

At the same time, the airline is in the best position to judge how expensive a seat-mile in any of their aircraft is. Engine cost can be calculated very precisely, so every airline should have a very clear picture of how expensive their twins and four-engined aircraft are.

There is a small chance that the geared turbofans which are now being introduced will give the A340 an edge over a twin variant. The higher thrust class of large twins makes a geared fan currently impossible, so a four-engined aircraft will have an edge because it can use a more advanced engine.