At RB and WR I usually don't do too much with my depth this early in the season, but wait until around week 6-7 to start making 2 for 1 offers to upgrade. Right now for instance, I have the following at RB/WR in a 2/2/flex league...
RB - Mcfadden, Murray, Lynch, Quizz, Pierre Thomas, Turbin
WR - Marshall, Harvin, Nicks, Stevie Johnson, Cobb, McCluster
As it stands now, I have to bench two of my top guys each week (this week I benched Nicks, oof). With that said, I can absorb an injury or two that a lot of teams in my league can't, so that's worth more to me than trying to upgrade a little bit at one position.
With that said, if a needy team comes to me looking to upgrade and I could sell off Lynch and Stevie Johnson for Ray Rice or Lesean McCoy, I'd have to think about it. I don't think having some depth is the worst thing in the world though.
At QB and TE, I will sell off my #2 if both options are performing well. Part of the reason I have Nicks on my team is because I traded him for Michael Vick when I found myself in a position where I had Matt Ryan and Michael Vick. If you have a guy that you only plan on playing once a year (in a bye week), or the two are close enough for it to be a coinflip every week, I don't have a problem with unloading my backup option. The same can be said for tight ends.