I just took a 2000+ mile trip in my 2006 GX on mainly flat highways, and played around with fuel grades for kicks. The premium cost more, but got much better gas mileage so it outweighed the cost.
Basically, in a modeern high-compression engine designed for higher octane fuel, the electronics will !Removed! the timing if you use lower octane, and you will need more gas to create the same amount of power as a higher octane gas would be capable of creating.
Most times, using a lesser octane (cheaper) gas will not save you money in an engine designed to use a higher octane fuel in the first place. Plus, the higher octane fuels tend to have a better mix of detergents/additives to keep everything running smoothly.
For instance, in one very long stretch of flat road, 91 octane "Premium" gas got me 18.5 MPG and 89 "Plus" got me 16.5 mpg... I went back and forth, and the results were the same. Didn't try the basic "low-grade" 87 octane.