I'd use the one on the amp vs HU. Set the amp's gain properly and omit using the HU. You have to remember, most of the distortion/clipping come from the HU. So opening up on HU to max will surely induce some unwanted results.
If you're clipping the amp it is, but setting the gains on the amp "high" won't hurt anything as long as as you don't turn the volume up on the h/u. How many people have the discipline to keep from "cranking it" however?
Bottom line: set the gains right to begin with
As far as then h/u's "settings" go, arbitrarily boosting EQ settings usually results in a less than desirable result. Its usually best to set things "flat" and then CUT, not boost, things to achieve a flatter in-car response.
Me? The only thing I boost is a bit of bass around 20 Hz with a 1 band parametric EQ to extend the frequency response of my sealed 10w0. Even then it would be better if I cut the output around this sub's peak response frequency, but as I don't have an RTA its just easier for me to do the boost thing around a frequency I know its lacking.