One way of reducing both pumping losses and friction is to remove some pistons and keep the corresponding valves closed. I did so with a little Fiat 127 some years ago, with 10-15% improved fuel efficiency. -Despite a lot more driving in high RPM:s to make up for the halved torque and rough running at low RPM. One thing I noticed shortly after the modification was that engine braking was decreased a LOT.
The resulting 525cc two cylinder engine with slightly above 20hp was probably a bit to the tiniest for efficient driving, since the need for hight RPM:s to get the power needed kept pushing the engine away and up from the BSFC sweet spot. In a modern car with more power margins I guess the increase in fuel efficiency could be a bit higher.
Projektblogg - Fiat 127 engine downsizing
Some years later I learned about "pulse & glide". (or "burn & coast", or "burn & glide" as I prefer to call it) Driving a 40 year Saab known for being a bit thirsty for it's size, I got far better improvements on the stock engine than I got from my earlier piston lobotomy.
For some months I was driving around with only three pistons "active" in that Saab's V4 engine, after an exhaust valve had been damaged. I simply removed the push-rods for both intake and exhaust valves to that cylinder, giving a nasty rattle from the lifters on some revs... I was expecting to get a measurable improvement from that cylinder deactivation but all I got was keeping exactly the same gas milage. Perhaps that damaged exhaust valve had some leakage, causing pumping losses that together with the frictions of the now "dead" piston, would even out the benefits from the increased load on the remaining three cylinders. After a while that engine suffered from some broken bolts, a loose starter and a cracked exhaust system, caused by the increased vibrations.
Somebody wrote earlier in this thread that engine frictions are play a major role in fuel efficiency, and that may also explain why I didn't get improved gas mileage after disconnecting one of four cylinders, but getting a rather nice improvement while ripping out two pistons and half of the valvetrain from the little Fiat, even though I wipped it a lot harder.
It would be interesting to deactivate half of the cylinders by inserting springs between the rocker arms and push-rods in an healthy old engine. Such a modification should spare the camshaft/lifters from nasty beating during the test, but also make it easy to get back to the stock engine again. The engine will still have a bit more than half the camshaft friction and full piston/crank friction, but the huge increase in engine load will reduce pumping losses and increase combustion pressure a lot during easy driving.