Definatly if your running sub/* I would turn off all base that comes from the interior speakers, hopefully you have sub control on your cd player or your just going to have to meet half way with the HU and the amp for the subs. I had the same problem til I got my new HU with sub control.

Don't turn out all the bass from the speakers. If you do it'll sound like it'* all coming from the back, and the mid bass will be gone.

Are your highs amped at all, or is it just your sub that is getting power. If it is just your sub dont worry about the mid-bass. You wont be able to notice it cuz of the sub anyways. Also youll have to turn down your bass gains anyways otherwise if the bass hits hard enough youll drown out your highs.