One thing is for sure, if you drive with the fuel gauge on E for an extended period of time, you will run out of gas regardless of what the time to empty states on the trip meter. I have found in my case that my manual calculations have matched perfectly with the average MPG on the trip meter. The miles to empty calculation is a bit off though since every time I run it down to 2 or 3 miles left there is never the same amount of gas left in the tank but usually its about half gallon that's left in the tank. So while I feel safe running it down to zero, I'm usually at the pump right when it hits zero or a few miles before zero.
I finally got the focus on the highway for long trip this past weekend and was totally impressed with the avg MPG. My outbound trip included a driving distance of approximately 350 miles and there was a two hour traffic jam that we went through. I made it on one tank of gas easily and averaged around 36 MPG and the miles to empty was around 65 at the end. The weird thing was the trip back average was 39 MPG (no traffic jam) but the time to empty got to zero prematurely and I panicked to get to a nearby gas station 45 minutes from home. As it turns out, the pump clicked off at only 7.6 gallons on my previous fill-up and I didn't realize it clicked off way too early. From now on I'm going to make it click off twice to make sure it is filled up or pay attention to gallons going in a little more.
I stopped at another BP station (I always use BP) and after filling it up, now the distance to empty jumped to 480 miles! I also averaged 42 MPG on the 45 minute drive home. Wow that was really impressive. Unfortunately, I'm back to city driving so I won't know for sure if I was really getting 42 MPG on the highway for hundreds of miles. Either way I'm very happy with the mileage on this car.