One of the fuel pumps burnt out -- if you have dual tanks, you can't run one of the tanks dry without damaging the pump in the tank. That's just poor design, but I was able to get the dealer to pay for it, which made me feel better.
Transmission had some odd shifting problems, which took a while to track down and fix.
4x4 also had problems shifting, which again took a while to get fixed.
Some minor fit and finish problems.
I inherited this truck from my father. It was pretty much his dream truck -- huge engine, 4x4, big tires, extended cab, all the options, etc, etc... He was a farmer, and this was exactly what he needed. He had nothing but good things to say about it in the time he had it.
However, I'm a 5' woman, and not a farmer. This is way more truck than I'd ever need. However, I'm sentimental, so I hang on to it.
From the standpoint of someone who actually needs a huge truck, it's great. It'll tow an amazing amount, and carry a whole bunch in the bed, too. I recently towed home about 5 tons of landscaping stone, and that big engine hardly noticed. And of course, all my friends call me when it comes time to move, which is always a good excuse for pizza and beer!
It also comes in handy when it snows 2 feet and the roads drift shut. As long as you use your head, the beast is unstoppable. I truly love cruising around in it during blizzards and pulling people out of ditches and such.
Gas mileage is terrible, as you'd expect. It drives like, well, a big huge truck. At my size, the cabin ergonomics are poor, and not all that comfortable. But I could say much the same for any large truck, I suppose.
Overall, it's way too big for me, and I don't much enjoy driving something that large. But it has come in handy from time to time. If you need a big, serious truck, an F-250 of one form or another is something I'd recomend.