Any sector profile is essentially made up of 3 segments, Climb, Cruise, and Descent. If the aircraft is flown at or close to optimum altitude, optimum cruise speed, and optimum engine Thrust Specific Fuel Consumption (TSFC), there's little to differentiate between the 2 and the 4 engined aircraft in the cruise. The major differences lie in the Climb and the descent.
The Climb is far and away the most fuel expensive segment of the flight, and the degree of climb performance (angle or rate) lies in the amount of excess thrust available, and, following from this, the best rate which is proportional to the excess thrust multiplied by the speed (Thrust X Speed equals Power). The 2 engined aircraft has far greater excess thrust in all phases of flight than does the 4 engined aircraft. This arises from the fact that both aircraft must achieve APPROXIMATELY the same performance with One Engine Inoperative, i.e. the 2 engined aircraft must achieve on 1 engine what the 4 engined aircraft achieves on 3. On the 99.999% of occasions that an engine does not fail (normal operations), the 2 engined aircraft now has a 100% increase in thrust above minimum requirements, whereas the 4 engined aircraft has a mere 33% increase in thrust above minimum requirements. Normal climb performance on the 2 engined aircraft is therefore far superior to it's 4 engined counterpart, and with it, a much shortened climb time. Thus, Climb fuel is much less, and climb is the most fuel expensive phase of flight.
Although I discounted cruise performance in general terms earlier on, there is a further consideration here, and again a greater degree of excess thrust will allow for climb to a higher, more fuel efficient altitude for cruise. Thus, cruise fuel performance is improved somewhat.
In the descent phase, all engines are operating at idle thrust. Whilst the flight idle thrust certainly extends the descent 'cheap ride' distance, the fuel expenditure for the idle thrust is very high due to poor TSFC at the much lower engine speeds. A lot of fuel for a little thrust in short. The 4 engined aircraft must tolerate twice as much fuel flow for little in return during the descent, than does the twin.
That's the comparison in a nutshell. It's a bit more complicated than that, but that's the simplified version.
Regards,
Old Smokey