the GS300 definitely gets better gas mileage. probably on average a good 7mpg, give or take. thats basing on epa values for the 2006 gs300, and what i've found in my experience of gas mileage on my 4r, which is a sr5 4wd v6. based on epa values of each, i'd expect an average of 5mpg better for the gs300.. even if the gs300 requires premium, which i think it does, but i'm not sure, you'd probably still be spending less on fuel for it than a 4r. the 4r also has a bigger gas tank, which means more gallons at the tank. you'd probably get similar miles per tank for each, but be using more gallons on the 4r than on the gs.
i'm pretty sure there are members here that have owned or own both, and would be able to give you a more accurate response.