There's folks that run hybrid defenses (press/man and press/zone, I did the latter when first starting the game). I dropped it a couple seasons after the engine changed and the turnover numbers dropped. I personally felt it better to have the minutes in the "second" defense distributed in the individual portion of the practice plan instead, but there are others who continue to run multiple defenses. I think it's just a matter of taste.
As for the second half of the question, if I'm outgunned at Ath and Spd, I slow the game down and try to control things via tempo. And then I hope the RNG gods are smiling upon me that night. And, honestly, if you're at a big disadvantage in both those categories, it likely doesn't matter if you're in a different defense.