Std Bore 318 with a Holly 80457 600 cfm carb, on a 2psp edelbrock aluminum intake, with a 268 cam. Going for best gas mileage, what size jets should I use?
IMHO, that cam is too big for that intake manifold. That intake has super small runners. Either switch it out for a weiand action + or an eddy performer, or move down to a cam in the mid to low 250 degree advertised range.
I have never noticed much difference in mileage by running lean. When you do run lean you will have to back off the spark advance and possibly slow down the spark curve to avoid detonation(spark knock). Ratarding timing is not much of an economy move. An adjustable spark advance can would be helpful when staying out of the fat side on the fuel curve.
If you want to play with it, I would move down in 2 jet size increments until it starts surging at a steady speed than go up one jet size and see what happens. Try reading the plugs after each tune too.
Usually there is a pretty fine line between economy and performance when dialing in the engine for street use anyway.