It's really dependent on the talent you have. I've seen coaches be stubborn to a certain system and it can bring a program's momentum to a halt, but then when your run too many offensive setups at one time it can confuse the kids too and it makes them not wanna try hard. It just depends but..
I prefer balance on my offense, that's the main description word of it, and I'd have a solid audible lineup depending on the defense and how they lineup. But my base offense would be 50/50 between run and pass with run my main focus preferably. I'd be out of single back sets, and the I, with some shotgun sets when I'm feeling snazzy. If I have more than 2-3 backs I'd consider wishbone here and there. I would run quite a bit of option if I have a QB who isn't a butterfinger lover or slow. He's gotta have the instincts first. If he can chunk it I'd let him pass as long as he has the guys around him. I have seen slow teams run the shotgun well; they just gotta be gritty and fight for the ball.
No matter what you have to run the ball to be a true working offense; when you can't you are screwed. So that's always my main focus in some form.
D wise.. I like to be able to blitz it besides that I'll let the DC have carte blanche over what he wants to run by who the team has to play.