Depends what we're talking here, actually recoup the money spent plus a sizeable savings in a reasonable time frame? I'd say that's generally a waste of time, say you spend $ 3000 a year in gas and spend $ 3000 to save 20% that would take 5 years just to recoup, and 20% over a well tuned engine would be huge gain.
Now if your talking decent mileage for a given power that's different cause hp cost dollars and doesn't over matter if it's recouped, still wouldn't go to crazy expenses to gain mpg cause over a certain point fuel mileage is hard to gain, My Avenger with all it's fuel mileage tech only gets 5 mpg better than my old 5th Ave and I did zero to get the best out of my 5th Ave.
For mileage I'd say besides a good tune and exhaust, cam cr gearing gonna be the lowest hanging fruit above that gains will tend to be small per mod and generally $$$ per mpg gain will go up. For NA power that won't overall kill mpg good heads will be best bet.