To make it the coldest put it on inside air, vent and high blower speed. I like cool air on my feet and face, but using that setting reduces the coldness of the air.
I typically start off with it on outside air, then after a few miles switch to inside and it really cools off.
On blower setting 3 it is noticeable in my 5 speed and I need to change my shift points. On blower speed 4 it starts to become a dog to drive. I dont really track my mpg, but just glance it at the screen on the dash. I see from 41 to 35 mpg.