I believe the combinations of formations makes a HUGE difference when doing this.
You need to match the offense with the defense, and also the run/pass.
To some degree you can think of it in real football terms, but for the most part, you need to experiment with your defense (and the players in it) to see what works and what does not.
I mostly use the 3-4 full time. With that I will blitz from every position, or not at all, depending on what offensive formation I am facing and what I expect them to do. Regarding the 3-4 it appears that you cannot get effective pressure on the QB without blitzing.