I've driven both. Both are good engines. The hp/torque for the 4.6L is 231 @ 4750/293 @ 3500. The 4.2L is 202 @ 4800/252 @ 3400.
http://www.fordvehicles.com/trucks/f-150/specs/#group10 If you are basically going to drive the truck like a car and not haul much with it and rarely pull light loads then the 6 cyl. would be good. But if you are going to haul stuff and pull moderate loads then I'd go with the 4.6L V8. Unless you have your foot to the floor at all times then your gas mileage will be MUCH better than any 6-8 mpg. I"m assuming you're looking at getting a 2 wheel drive. You should be able to get 20 mpg on the avgerage from a combination of city/highway driving. Personally I would recommend the 4.6L V8. The gas mileage is going to be pretty much the same for both of those engines. The V6 has to work a bit harder than the V8 to move the heavy truck so it's not going to get much better gas mileage. In fact I believe the EPA estimates for mpg's are pretty much the same on the window stickers, too. Go drive both and see what you think. I liked the better power of the 4.6 over the 4.2L.
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1994 Red SVT Lightning #2019