Even with a WDE/EDGE who isn't 265-300+ pounds, I get nervous about those types of players being in a position where they theoretically might be forced to cover a slot receiver or running back coming out of the backfield in the open field. As an OC I'd try to get that matchup as frequently as possible.
The multiplicity you mentioned is one of the main reasons why I prefer the 3-4 or 3-3-5 over the 4-2-5. You can have your linebackers, who will typically be substantially better in coverage than your lightest/most athletic linemen, all drop into coverage and pick any of your DBs as the fourth rusher.
If you want to get really weird, check out simulated pressures (look at Dean Pees- there's a great example of a simulated pressure against the Browns a couple of years ago that caused a forced fumble) and creepers, which can do a great job of messing with the OL and QB, especially when used creatively with exotic blitz packages.
In the example I mentioned previously, Pees used a 2-4-5 simulated pressure package where he had something like 2 linemen, 3 linebackers, and a safety all lined up at the line of scrimmage, and at the snap, 2 LBs and the safety sprinted back into zone coverage, while the 2 DL and a linebacker rushed. This also disguised the nickel corner blitz, which went almost untouched through the OLine (and I believe might've forced the fumble).
I'll have to see if I can find the video and post it.
