It's not all that straightfoward. If you're on the highway with cruise control on, you want to have higher vacuum because this means you're burning the least fuel. However, consider this example BSFC chart for a Ford 2L:
How to read this chart: The contour lines show how many games of fuel are required to make one kilowatt-hour of energy, or in other words, how effectively the engine is converting gasoline into usable energy. More grams to make 1kWh means more waste, so lower is better on this chart. Notice that the engine is most efficient at high load (close to wide open throttle) at lower RPM - so, even though it's burning more fuel than if you used less throttle, it's burning it more efficiently.
This is part of why pulse and glide works - you're running the engine in a more efficient range (low vacuum), but that would cause you to accelerate out of your target speed, so you cycle the engine to maintain speed.
Another example, taller gearing improves fuel economy, but also causes vacuum to decrease.