If you're looking for increased reliability or comfort then it may make a difference, depending on where your saddle is on the post.

If you already max out the saddle in a particular direction (say it's totally pushed back on a zero setback post) then getting a setback post will put the load in the center of the rails, not at one end. This could improve reliability, especially for those rails that actually say "No" at either end of the rails.

If you get a setback post it could be much more shock absorbent. VeloNews did a test measuring deflection/comfort and found certain posts to be much more forgiving than others. I don't remember specifics but I think all the comfortable posts were setback posts.

Therefore if you're looking to improve comfort at the back of the bike then a setback post may improve that.