Fuel saving approaches.....
From a practical point of view your range of efficiency options is usually limited...say 1,000 RPM to 1,500 RPM or so for 2 cycle Detroits...Planing at high speed/high RPM in our heavy hulls isn't efficient nor is trying to creep along at four or five knots....so the mid range option's involve slight engine efficiency trade offs with significant hull efficiency improvements at moderate speeds. Hull speed rules.
The practical answer is that for most of our hulls in the 45 to 58 foot range likely 7 or 8 knots would be best, but that's a bit too slow for my 8V71TI's/48 YF....engines...exhaust temps would be too low...so a compromise at 8 to 11 knot range depending on HP, length, etc is about a good as it gets....maybe naturals have a slightly larger cruising RPM range choice. In my case 10 to 11 knots balances all this.
HOWEVER: if you cruise in tidal currents, running with the current instead of against the current can make a significant difference.....In eastern LI sound for example, (especially Plum Gut and along the LI shore east of Mattituck) currents run over three knots....so if you get your lard out of the bunk early and run with the current you may gain 6 knots versus sleeping til noon and opposing the same strength current.
In Maine, if you are running into bays,estuaries, rivers, do so on an incoming tide....tides vary there over ten feet, closer to 12 feet "down east" and while the currents are usually moderate, it can make a difference when running for several hours. The "mighty Kennebeck", for example, has strong tidal currents.
(That's the river featured in the TV documentary of an Arleigh Burke class destroyer being launched and run for a shakedown cruise....from the Bath Iron Works)
The other main thing that comes to mind: clean running gear. Keep props and shafts and rudder clean of mussels and barnacles, for efficiency. Keep underwater intakes clear for proper operation of machinery.
And has been discussed here in other threads, large diameter props and oversized blade area can help efficiency at moderate RPM.
If you do not cruise in tropical temperatures where a genny must be run for A/C, traveling every few days can also reduce genny run time and genny fuel use. Instead of an all day trip, for example, every five or six days, a run of a few hours more often heats water, charges batteries, and may help keep the boat warm in cooler cruising weather...all of which might reduce genny run time, wear and tear and fuel consumption.
Another option is to keep a portable gas genny aboard. I have a 4KW gas genny under a fabric cover in my cockpit....I use it to charge batteries in hot weather which keeps big diesel genny heat out of the boat....I originally bought it for cold weather cruising security...one pull and I knew I would have power.... but I found it smart to use it for light duty in hot weather. Now that gas is cheaper than diesel, this makes even more economic sense.