Is the same effort required to maintain a set speed using different sized chainring / cog combinations with same ratio
Here are some points taken from the literature:


Mechanical efficiency is usually 88-98% for majority of deraileur systems (when clean,lubricated and new)
Drivetrain efficiency decreases with smaller rear cogs,
Highest efficiency can be reached at high torques and low cadence,
Chainline effects are negligible, imposible to note with measurement apparatus,
Higher efficiency can be obtained with a single-speed as opposed to derailleur use, and there may be a few reasons for this.
Efficiency of an internal gear hub is generally lower than this of a derailleur system*


So in your case it's likely that the 48/16 setup will give a slightly higher mechanical efficiency. Also once you've gained the desired speed higher rotational inertia of larger sprockets will help keep the speed at slightly lower effort. On the other hand lighter and smaller sprockets will make it easier to accelerate. However all these changes will be barely noticeable on the road, and especially when the drivetrain is already worn.

Some research has been done in the past on this topic, and there are also pages like this one, where the data on resistive forces within the drivetrain can be bought.. 



*Reference: Wilson, David G. Bicycling Science 3rd ed. 2003. p. 342-344