Here's a base-specific fuel consumption chart for a Prius engine:
Here's one for a more traditional Saturn engine:
Source:
http://ecomodder.com/wiki/index.php/...on_(BSFC)_Maps
In brief, higher cylinder pressures are more efficient, and generating vacuum wastes energy. There's also a best RPM for each engine geometry, which has a lot of factors but probably has a lot to do with flame speed vs piston speed and the fact that friction goes up exponentially as RPM increases.
In a perfect world, an engine would be able to operate at its best RPM and generate no wasteful vacuum. Unfortunately, the power needed in a car is highly variable, while engines are only efficient in narrow windows. Engine sizing, then, is very important.
In a vehicle with fixed ratios, increasing vacuum does indeed reduce the fuel burned, but you're also losing efficiency. It would be better, rather than running at higher vacuum, to have a yet taller gear and keep vacuum low. After all, doesn't upshifting always hurt economy? And downshifting help? But it reduces vacuum? If high vacuum we're good, you'd always want to drive around in first gear at redline to make the most vacuum possible.
In something like a Prius, where engine speed can vary effectively infinitely, the throttle plate is left wide open and engine speed is varied to produce the power needed to move down the road. Diesels are more efficient in part because they generate no vacuum, but instead have a variable air:fuel ratio.
Many engines start to enrich AFR near wide open throttle, which is a large part of why peak efficiency is often just below that, rather than at it.
Systems like variable valve timing and cam lobe profiles are examples of technologies which make the high efficiency windows larger.
If you wanted to run your engine at high load all the time with fixed gear ratios, you would, unfortunately, accelerate past the speed limits, because most engines are oversized so you can still climb hills and such. Many on here practice a technique called "pulse and glide", whereby they accelerate, then cut power to the engine and coast for a bit. This isn't always feasible, but it usually provides large returns. My previous car had stupid gearing and would deliver ~30mpg at 45mph, but could average over 50mpg with very dedicated pulse and glide averaging the same speed.
Hybrids oversize the engines less and provide burst acceleration assistance with an electric motor. My Insight's gasoline engine actually varies air:fuel ratios too, to a limited degree, which allows diesel-like efficiency in some cases. Hybrids also get rid of a lot of lossy accessories; my car has no power steering pump or alternator. For these reasons (and more) I can see 100-120mpg under optimal conditions, without the need for many driving techniques. For you, there are a lot of tricks you can use to overcome engineering limitations and improve economy. Driver technique often provides more return than any modification to the car.