Watch the Rig Setup online guitar lesson by Jeff McErlain from Blues Survival Guide: Rhythm Edition
Your basic classic blues tone is not too over-driven. If we look back it was really the blues guys who first started using distorted amps. Most amps in the 50's were pretty low wattage so they would crank them and bam, rock and roll was born. The awesome side effect of the over-driven amp was increased sustain that we all love. A good blues tone starts with a slightly over-driven tone that reacts well to your pick dynamics and cleans up well with the volume knob. Of course there are exceptions to the rule, for example Jimmie Vaughn basically plays with a clean tone and Gary Moore played blues with a pretty distorted lead tone. But for me the base tone is always leaning toward the cleaner side of overdrive. If you listen to one SRV's tone (one of the best and most copied ever) it was fairly clean even compared to Clapton's Beano tone (one of my favorite tones ever). So it is a personal taste issue, but you do want as much note clarity as possible on your chordal work, that usually means less gain. Added benefits of less gain is that you cut through a mix more easily.