Best possible mileage?

And I've read about people monitoring their AFR to properly tune their cars. Is that really necessary for a street driver that isn't running on the edge of the performance envelope?
No.
But the thread title is "best possible mileage?"
Driving on the street sucks gas no matter what because the throttle is constantly jumping around, as you speed up/ slow down/brake/turn/and start up again; and if you make it too lean, it will be even worse.
In town, getting your PowerTiming, and Part-Throttle timing will be much more important.
I think I mighta said this already, but here it comes again;
Every gas burning engine has exactly one crank position that is the best place for peak combustion pressure to occur for maximum energy transfer to the flywheel; which is typically 25 to 28 degrees ATDC. All your timing systems should be engineered by you, to make that happen under as many circumstances as possible, as regards EngineSpeed/(rpm) and Density/(AFR).