Runes and health penalties... always worth it?

Are any health penalties worth it if the rune is for a skill that you use? IE: I use expertise, marksmanship and wilderness survival. Applying 3 superior runes removes 210 health total from my character. That seems like a hell of a lot to me... is this wise? If runes are so damaging to health, is it always a sure bet they are worth using?

The best strategy is to use 1 superior rune to augment your best attribute (the attribute that would affect the most skills in your bar), 1 superior Vigor rune to offset the health loss by 50, and minor runes for all your "inferior" attributes. Of course, this doesn't include secondary class attributes since you can't use their runes anyway.

I suggest reading the first alpha round table discussion in the articles section. They answer your question really well.

The short story is that there are sweet spots in those skills that you want to shoot for. They settle on a major rune in expertise and minor in marksmanship, for a 13/12/8 setup.