After years of driving Honda Accords and having an older, beater Ford work truck around for weekend projects, I decided to take the plunge and support the "home team", as the F-150 is produced locally. Ironically, my best friend recently switched from longtime domestic truck/SUV ownership, to Toyota...
The regular cab has small "pocket" doors, which are convenient and easily accessible, but I have noticed the doors rattling over bumps, which may necessitate a trip to the dealer to have them adjusted.
The seats are comfortable and supportive over long trips. I recently towed a Kendon trailer with 2 full-size motorcycles, gear, and a 200+ pound passenger, 2400 miles round-trip from Kansas to Montana. The gas mileage was in the low/mid-teens with an Interstate cruising speed of 70mph and tire pressure at 40psi (I didn't realize until later the OEM tires' max cold cap. is only 35psi!). I've seen 20mpg at 65-70mph on solo, unladen trips, and I've noticed the truck has excellent coast-down, which may be credited to a combination of the all-season Michelin tires and lower drag of 2WD. My truck has a 3.55 limited slip rear end.
I would recommend a spray-in bed liner, such as Line-X, for sound absorption and bed protection. Also, the interior of my truck is light grey, which shows dirt/stains, so regular cleaning and/or a fabric protectant is recommended.
The optional AM/FM/6-disc CD/Sirius Sat Radio head unit with auxiliary jack is of decent quality/sound. I can plug in my MP3 player/GPS unit and play them through the head unit.