good question - but yikes, too many variables.
I'd say (1) pick a subject you have an interest in already, because you're going to be spending a lot of your life thinking about it. and then proceed if (2) it has large enough searches or (3) a really high CPC in some aspect.
then for this subject, pick the best name to your budget that has - if possible with (4) high resale (5) high wordtracker (6) high existing traffic, etc etc - the best your budget can afford.
and you have to have a cool concept/ design in presenting it!
personally i don't develop my highest resell names, as i want these available in the markets and i want to keep my developed sites indefinitely. i pick the most brandable/ memorable names for myself, and with these you can add the most value with a great site anyway. besides, uber generics i often find a little bland, and if it's good enough for google, yahoo, ebay et all.
:sold: