note that setting gains by the DMM is one tool. you may end up going a bit higher or lower. blindly setting gains by this method is a start -- it gives you maximum power without signifigant distortion. but this may not be your goal. in some cases you may want less then maximum power, you may not be as concerned about distortion from the amplifier, or the system distortion will be from the speaker (and in excess) in which case maximum power without signifigant distortion will be limited by the speaker even if the amp is capable of happily driving the speaker beyond its limits.
lower gain (higher voltage marking on the gain-knob) if the speaker being amplified is too loud or has signifigant distortion.
higher gain (lower voltage marking on the gain-knob) if you are not worried about damaging the speaker and can tolerate the negative effect of distortion in exchange for the (arguably) positive effect of "compression". amplitude compression is a lack of "dynamic range". basically the more you compress, the less difference you have between loud and soft notes. cranking the gain will make soft note louder, but will distort loud notes.
sonically, one can argue that the increase in average loudness is worth the addition of a little distortion. from a power point of view, you may be able to damage your speakers -- especailly if the distortion can affect speakers not made for high power (such as tweeters). many factors come into play though. there is a chance of equipment failure, and thus highly excessive gain is discouraged even if you don't care about distortion.