The replies in this topic are all excellent, and I'd heed their advice. I'll throw in an anecdote:
When we got our 5th wheel, a 25', 5400 lb dry weight Jayco with no slides, we bought a new Dodge 1/2 ton. Ordered it SPECIFICALLY for towing. 2WD 'cause it had a higher tow rating, 360 with the 3.73, and so on. On the flat's it was fine, although mileage, even with our small, low 5th wheel was often down in the 6mpg range. You also had to take it out of OD any time there was even a slight uphill and stayed pretty much in the right lane at 65 mph or less.
First time in Colorado, we headed up I-70 to the Eisenhower tunnel, and quickly found ourselves in first gear, at 20-25 mph with foot to the floor. It climbed, but it wasn't comfortable. Over the 5 years we had the Dodge, the rear end was rebuilt, the engine had a number of problems, but the transmission survived (I was told we'd destroy the transmission first). At 105,000 miles, after getting the truck back from the 9th visit to the dealer for engine problems - this time they decided the heads were "bad" and replaced them (this was the ONE time I can ever remember the extended warranty being worth the cost! It expired at 100K and we replaced the truck at 105), I replaced the Dodge with a 2005 Chevrolet Duramax.
The difference is incredible. On the flats, the trailer is invisible. At 60mph we get 14mpg. At 70 (a speed we never were able to drive with the Dodge) we get 10mpg. My wife, who does the vast majority of the driving, is infinitely more comfortable and confident in the Duramax. AND, on I-70 heading for the Eisenhower tunnel, we now easily run 55-60 mph and the truck doesn't even shift out of overdrive.
Yes, the diesel was more expensive. And it probably isn't any cheaper to operate. But the peace of mind is worth it to us. We're at 150,000 miles, towed trailer approximately 40,000 miles with this truck, and we're now looking at going to a SLIGHTLY longer, slightly heavier 5th wheel that's nicer, and I'm not at all concerned about the tow vehicle's ability to handle the new trailer.