I have trips between Lacrosse and Milwaukee (220 miles) on a bi-weekly basis. I recently archieve slightly over 40 MPG, which suprised me alittle bit because I am not using a low rolling resistence tires.

My tires are around 33 psi, filled with nitrogen.
I am using 5W-20 engine oil.
i am using goodyear responseEdge tires (Non low Rolling resistence).
A/C is on throughout the whole trip
I use cruise control.
i set the speed around 68 (according to the speedometer)
I am always the only one in the car.

Right now my car has travelled 34400 miles.