Hybrid Runes?

Obviously no. Lethality is a scaling stat, and you would want the pen for the early game, when your autos do decent damage.

I would say yes, but only for specific champions. For instance warwick right now deals about equal magic and physical(at least the way I build him) so the penetration hybrid runes are good on him. Also you could build nunu in a way where they could be useful on him as well, but he probably wouldn't be optimized then. Basically just for championsale that are going to do a combo of physical and magic damage, Nunu and Warwick are the only ones I know I have thought of buying them for.

Oh, somehow completely missed the word mage in there, I feel dumb.