Re: 4.2 vs 4.6
I drove a truck for a week until the owner sold it as my company van was in the shop. It was an older STX reg cab, 4.2L V6 5 speed manual, and it got great mileage. I can't speak for the automatic version but on a sheer displacement and cylinder count, the V6 will net you better mileage, lower maintenance costs throughout it's lifespan than any V8 will. If you plan to tow or haul on a regular (daily) basis, then get the V8. If it's just you in the cab with the empty bed, the V6 will not disappoint.
Be sure to check the axle ratio (generally on a sticker in the glovebox). If you plan to drive highway miles for the most part, get a taller ratio (3.55/3.31) versus a lower ratio (3.73). If you plan to drive around town and on the highway than any ratio will be a good compromise for mileage, as a lower ratio will get the vehicle up to speed quicker, so you use less fuel.
The big reason that Ford offered the V6, was for fleet/work use. It was economical for Ford to build, and cheaper for the consumer to buy for those who required the use of a full size truck. It could also be had with a manual transmission to lower the cost to the consumer even more. The V8 was produced as a low cost alternative to those buyers who needed the extra towing capacity, or the use of 4wd.
The V8 is a smooth engine, but it lacks refinement in the upper RPM range (at least the 4.6L 225hp version in my '06 E-Series does). With mostly highway driving I was able to get 12L/100km or roughly 19mpg with 4.10 gears in good weather. I would have preferred the V6 as the torque peak is lower and only 35lb ft less over the V8; however, Ford no longer offers the 4.2L V6 in the newer E, or F series. Whatever engine you choose, parts are a plenty! For owner reviews check out autos.msn.com
'00 Durango R/T 360ci 290hp (modded); 138,500m
'06 Pontiac G6 GT 3.5L 220hp; 44,000m
'12 Chrysler 200 Limited 3.6L 283hp; 13,000m
'99 Taurus 3.0L 2V Vulcan 145hp; 154,300m - Traded
Amsoil in all vehicles!