I think a good mass flow based EFI would allow more precise fuel metering, which would allow any engine to run leaner, without issues, than you can get with a carb. It will also allow tuning the spark to get the most power out of the fuel being burned. So, yes a good EFI, properly tuned, would squeeze more miles out of a gallon of fuel. That being said, it can only be tuned to the engine it is on. Old Big Block engines have a lot of friction and pump a lot of
oil. EFI can do nothing to help that. If EFI gave you a 10% increase in power, on a given amount of fuel burned, a 10 MPG engine would increase to 11 MPG. In other words, you would hardly notice the difference.
If you added EGR, you would likely see much more improvements, as it will allow you to pull in more timing without pinging. I'm not sure that would work so well with a lot of cam, but should with a milder cam. I just do not think the benefit would be worth the hassle and ugliness under the hood. At some point, it makes no sense being on a Cobra.
Speed density and Alpha-N type EFI, I doubt could match mass flow. On a mild engine, speed density could come close enough. Alpha-N is not nearly as accurate on fuel.