I run a ton of 3-3-5 but do so in the split formation, which leaves the safeties on either side of the formation close to the line. I love having the safeties in run support, and CB is the defensive position I focus on most, so I can often find some stronger guys to convert to safety who are capable of providing run support but can also line up man to man against any receiver. The lateral run game is absolutely shut down, and while a north south run game can have some success, tackles for loss come often enough in this defense to stall out drives. It can be a little spotty against crossing and quick cutting routes in the passing game, but unless it is third a long, when having two deep safeties help out a lot, it's effective enough as anything else against most passes.
A lot of guys here run a finesse running game. I look for pocket passers, so my QB's don't run, and I tend to keep things simple by letting my guys try and find a gap for 5-6 yards in the middle, or use a power O or stretch play with a speedy guy to get outside the defense. I run a committee backfield, so my speedy guy takes the outside handoffs while my bruiser pounds his way up the middle. I maintain a very effective running game by not trying to do too much and just letting my guys pick up the yards that are available. Short yardage is the primary goal there, and everything else is running out the clock or letting my passing game do the work. I only need to complete 1/3 passes to keep a drive going, which can be accomplished most of the time even with QBA at 5 and brutal pass rush.