Gary,
My view is that you rough tune fuel to avoid harmful conditions like detonation or extreme richness by looking at the plugs, exhaust, and listening to how the engine performs.
Then you fine tune to optimize performance. This can be maximum horsepower, bes throttle response, best fuel efficiency, 'safest' fuel, or all of these (in different areas of the fuel table). To do this, you need to study the spark plugs, and have an objective measure of the target you are tuning for. This means a drag strip, dyno, g-tech pro, a good stop-watch to check 20 to 70 time, or something like that. An experienced driver helps a lot, and will be able to feel even the effect small changes in AFR. People with less experience will have to rely more on objective measures (until they gain enough experience, knowledge and sensitivity).
Always start at low loads and rpms, tune those, then up the rpm and/or load only when those are running right ("what the engine wants"). This does three things:
1 - it hopefully prevent you from breaking engine parts,
2 - it allows you to gain experience in less crtical tuning situations,
3 - it encourages you to use the existing tuned areas to tuning the new areas (i.e. you make smooth changes in the VE/AFR tbale values as rpm and load changes).
There are a number of 'rules of thumb' that can help (12:5 at peak horsepower, 13.1:1 at peak torque for a naturally aspirated engine, etc. But as Al says, these may not be right for your engine (but they may not be a bad starting point for tuning either)).
There is more on this here:
http://www.megamanual.com/begintuning.htm#symptoms, but it's not a bad idea to read that whole page as well as this:
http://www.megamanual.com/ms2/tune.htm
Lance.