Base specific fuel consumption charts are basically what I base this off of:
https://x-engineer.org/automotive-e...ormance/brake-specific-fuel-consumption-bsfc/
These charts show how efficiently an engine can produce an amount of power at various RPM and throttle. In the above image, the blue isolines represent fixed power output across rev and rpm range. They tilt downward to the right because engines are typically less efficient at higher RPM, and they curve because engines are typically less efficient at lower load.
If it takes ~20HP to cruise down the highway at 65mph (a very reasonable figure for a mid-sized sedan), running the engine at 2000rpm gives a BSFC of around 240g/kwh. At the same rpm at wide open throttle, it's about 200g/kwh, which means throttling is causing a 20% loss in efficiency here, for various reasons beyond the scope of this post. Of course, at WOT you're producing more like 50hp so you can't maintain a fixed speed and stay in this peak efficiency island.
To make matters worse, a car with a traditional automatic or manual mated to a 4 cylinder is probably not going to be geared for 2000rpm @ 65mph; 2500-3000 is more common, because it gives you extra passing power without the need to downshift, and prevents the car from feeling "underpowered". If in top gear the engine spins at 3000rpm, to produce 20hp, the engine in the chart above is at an abysmal 320g/kwh. Or in other words, it's burning around 60% more fuel than if gearing would allow it to run at 1400rpm @ 65mph (producing the same power)
CVTs are nice from an efficiency perspective because they have effectively infinite variability of RPM and load. They're generally programmed (unless you hit paddle shifters) to keep the engine at its optimal load vs RPM to produce the power you're asking for. The red line in the following image shows where a Prius engine is allowed to run by its orbital gear system:
So, throttling losses can be very significant, and picking an oversized engine with limited gearing can hurt fuel economy tremendously.
If you're using the engine in the first image paired with a traditional auto or manual and driving at 10,000ft vs at sea level, air pressure is only about 66%, meaning when cruising you'd be running much closer to that island efficiency; lower air pressure is effectively the same, from an efficiency standpoint, as downsizing the engine.