The 2008 F250 in my sig has the 5.4L; I changed from 3.73 to 4.30 in the axles and, to me, the difference was quite noticeable and since a great majority of my driving is non-freeway, the MPG loss is virtually non-existent.
Want me to be honest? I like the truck but if I could do it over I'd hold out for a V10...and I'd hold out for a Lariat this time but that's another story. I get an itch for a new-to-me truck every 2-3 years anyhow so I'm selling or trading it this summer and am strongly leaning toward giving Ram a try as I really like their current generation of trucks.