I have had 2wd trucks and 4wd trucks and in the last 15 years, I have actually only needed to use 4wd a few times. The thing to note there though is that I needed it. There were also a few times in my 2wd trucks that I wish I had it so that I did not have to have someone push or pull my truck out of snow/mud/sand.
I look at it like this, the price difference is small and when in 2wd the prop shaft is just floating since the front axle is disengaged and the transfer case is disengaged. This means there is very little drag so no wear on the 4wd hardware and almost no effect on fuel economy. Yes there is a slight weight penalty but the difference on a 3500 is marginal. You know what they say, better to have it and not need it than to need it and not have it. That being said I would not pass up a great deal on a used 2wd truck but if I was getting new I would get 4wd.