You should be designing the sub + enclosure combination so that the natural frequency response is as close to ideal as possible. Generally this means aiming for a flat response before the "knee", a -3dB point of 40-50Hz and 12dB/octave rolloff.
After this, then set the amplifier level to match the rest of your system (bass/treble levels equal) and then tune the crossover point so the sub blends properly with your other speakers.
You should not be using the amplifier to band-aid a poor enclosure/speaker match by ramping up the gain. If your speaker is not matched to its enclosure and you try and correct it using the amp, then you will be pushing much more power at the speaker than you need to and it will fail.
some light reading for you:
http://www.bcae1.com/spboxad1.htm