Several scenarios:
Summer:
In the Targa I run with the windows down when I'm moving slow <55mph. On the highway ~80mph, I HAVE to roll up the windows because the wind noise is so freaking loud!
Winter
Generally, since I bought it 1 year ago, I drive as often as possible with the roof off (which is why my top is so beat to hell). I will roll up the windows if it's cold and turn the heat on full blast. Makes for that wonderful "feet sweat-hands freeze" scenario.
Exceptions:
If it's really hot out & sunny, I might put the top on to avoid "head burn." The follically challenged know what I mean. I found this out the hard way. Sunburn on that which does not see sun is a recipe for a stomach ache. (I'm not kidding). In those cases the windows are defintely down.
If I really want to be a p****, I will run the a/c. And I will only do so in places that Pari or the other Dorkis are guaranteed not to see me.