It's your truck, you have to live with it. Most of the people who settle for the smaller motor without regrets never have to ask advice because they know what their needs are, they know what will meet them, and they don't need or want a hot rod. The people who ask and agonize are worried about how much they're giving up to go smaller, a sure sign that the bigger motor is a better bet in their case.
Based on real world conditions, all will depend on how the truck is driven. I have managed 18.7 on long road trips with 60-65 mph cruising speeds in my 09 Crewmax 5.7 4x4. 1-2 mpg less than what a 4.6 is supposed to be capable of in the right configuration and driving conditions. But mine is one of the heaviest versions of the truck and I'd do better if I kept her to 55.
People have posted on here talking about how disappointed they are that they can't do better than 17 or 18 mpg in their 4.6 at their normal 70-75 mph cruising speeds. There are tons of people who, like me, can match or come close to matching the 4.6's rated numbers in their 5.7 if they drive it right. The 4.6, when driven in the real world like alot of people drive, going stop light to stop light, flooring it to merge, and cruising at 70 mph and above, won't match its rated numbers. And any supposed advantages will diminish even further. The 5.7 just won't work as hard under the same circumstances. The mpg advantage isn't always about smaller displacement. It's about horsepower to weight ratio and rpms.
I would probaly think it's safe to say you can buy the bigger engine and get the mpg difference between a 5.7 and 4.6 down to almost nothing if you know how to drive. But there is nothing you can alter in driving style and conditions to pull another 70 horsepower and 75 pound feet of torque from the 4.6 when you need or want it.
It really comes down to initial purchase price and what you want to live with. Having something impressive happen when I dip into the go-pedal is important to me so the 5.7 was my only option. If you go for the small motor it should be beceause you don't care about or need the added capacity and performance of the 5.7, not because you want the bigger engine but don't want to spend more money. Life is too short and vehicles are too costly for you to settle for less than what you'd really like to drive day in, day out for the next 3-5 years or longer. Cheaping out on what you really want can actually be more expensive in the long run than spending more money for the right truck. Just ask people who are in a new truck every 1-3 years because there is something else on the option list they just have to have that they don't already.