The days of the four-engine passenger aircraft are certainly numbered.
Airlines are more interested in convenience, frequency and efficiency. The new Airbus A350, along with market incumbent, the Boeing 777, will be a commercial triumph - the vast majority of all long haul traffic in 2025 will occur on these airframes. The A350 has already 780 orders and the 777 close to 2000 orders now after being in service for over 20 years already.
Operators are also looking to operate into new markets all the time - however these routes obviously can't justify a 400-seat aircraft operating return daily.
Oh... and building an aircraft that you can only operate within 10% of the world's airports without modification is great commercial planning!