The short answer is that yes, you can change your differential to optimize fuel efficiency. CAVEAT: it is almost certainly not worth it.
Here's a very high level discussion of why there are better ways to achieve the same goal (better fuel efficiency):
Think about how the air-fuel mixture in the engine is managed: for each revolution of the engine, a unit of air is sucked into the cylinder. A unit of fuel is added to this air according to the ratio set by the fuel regulator (an engine computer, a carb or functional equivalent). This combination of air and fuel is then going to be compressed and combusted.
However, that squirt of fuel was your entire fuel consumption: that's the only time that fuel leaves the tank on its way to being ignited. If you want to manage your fuel consumption, you want to reduce the number of times that injection happens and also keep the amount of each injection down.
So, you have two things that you can manage, one of which was the topic of your question:
Gear ratio: a high gear ratio allows you to cruise at lower engine revs (your real goal). This reduces the number of fuel injections per second. The gear ratio can be changed by modifying the vehicle with a higher final drive but it is significantly more convenient to just select a higher gear. Barring that, you can also purchase larger diameter tires. Try driving in 5th gear (an overdrive gear from your notes above): is the engine speed close to your comment of "one you can run without the engine struggling"? If so, you are done.
Throttle position: an open throttle allows more air into the cylinder. As a result, more fuel is added to preserve the mixture. The least throttle required to move is almost always the most efficient throttle position. This is also why leaving the vehicle in gear during decelleration is more efficient that moving to neutral: the vacuum generated will result in even lower fuel consumption than the idle setting.
Practical example: in Top Gear season 4, Jeremy Clarkson drives a turbo diesel Audi from London to Edinburgh and back on a single tank of fuel. That episode summarizes almost everything you need to do as a driver to maximize efficiency. Some of them are a bit extreme (e.g., never turn the heater on? I'll pass) but others are practical and applicable (e.g., management of momentum and situational awaareness).
