Proper gear calibration is key.
Once you have your line level sources setup with proper operating limits and no clipping on the output, you can next move to the amps.
You should never run your amps full tilt unless you have calibrated them and you know that the output voltage on the amps speaker terminals is within the operating range that your speakers can handle.
You can calculate the maximum voltage that your speakers can take, and then set your amps with a multimeter so that under normal conditions you should not be going over that maximum voltage on the outputs so your speakers will generally be safe. If you increase the gains even more you risk any spikes going through and over driving your speakers causing the mechanical limits of the speaker to be exceeded resulting in failure.
Eminence has come out with a product called d-fend that guards against this over voltage allowing you to play within the limits and not worry if you do have a spike which can sometimes be harmful to your equipment.
http://www.eminence.com/d-fend/Proper setup of your equipment from laptop to mixer to processors to amp is key. Its not something that should need to be tweaked. Once its set the only thing you should be adjusting is the volume on the mixer.