Yes, you could absolutely modify the final drive gearing, or put a larger circumference tire on an FJR and it could handle it, but gearing, like almost every other part of life, is one more in an endless series of compromises. You would absolutely get lower rpm at a particular road speed, but other than the needle pointing to a different spot on the tachometer, what does that really buy you?
Do you get a proportional increase in fuel economy? I would suggest that you do not. You may get a minor improvement in fuel mileage, but not the same percentage by which you alter the gearing. There are far too many other variable at play for there to be a 1 to 1 relationship. And, at what cost do you get that mileage?
You will absolutely have worse acceleration in all gears, since the final drive affects the gearing in all of them. Low speed becomes trickier with higher overall gearing in 1st gear and youll need more clutch slipping in parking lot manouvers. And roll on in top gear will be more sluggish, amplified by the 5th gear overdrive ratio.
Smoothness of the engine, and reduction of vibration at cruising speeds is one reason often quoted, but There is a wide range of perceptions and personal tolerance to vibration, and also apparently some variability between bikes. I find that my FJRs have tended to smooth out somewhat when rpms are raised up above around 5000, which coincides with FJR nominal cruising speeds of 85 to 100 mph in stock gearing. The harmonic misbalance of the in-line 4 FJR engine seems worst in the 3500 to 4500 rpm range.
In essence, the increased final drive ratio that occurred between the quicker 1st Gen bikes and 2nd Gen and later bikes is tolerable, but also quite noticeable to anyone sensitive to performance. Like all of our other compromises in life, there is no such thing as a free lunch.