I think the runes work on a cooldown system, not a normal resource system. So if each rune has a cooldown of 10 seconds, and there's 5 runes, so if you have 1x frost, 2x unholy, and 2x blood, you can use a frost spell and wait 10 seconds, or use an unholy spell twice in 10 seconds, etc.
I also think that if anything, the runes won't take up much space. It seems to me to be more of an ability (you just etch them into your sword or something like that) that may take up 1 slot with an item (e.g. box of runes), rather than actually having the runes. If they do take up space, likely they will stack to 20 or so, so you only use up 3 slots.