If I cast a Rune or a Fireball and it kills five people, does it only raise the skill for casting it once or does it give more XP for basically killing five people? Asking so I know whether I'm better off just picking people off one by one.

I'm under the impression that experience is calculated by damage done. This would mean that killing two critters with a single fireball, and killing the same two critters with two separate fireballs, would result in the same amount of experience - but the former would be a more efficient use of magicka.

However this is just speculation on my part, I don't know how I'd go about confirming this. I'll also note that moderators are non-employee volunteers.

Maybe test it by setting up a scenario where your close to leveling, see if one way or the other, you gain enough to level or not. Otherwise im not too sure.

I am not sure. A tip though, another way of increasing the Destruction skill is to use Conjuration (conjure a familiar etc), that's how i got my destruction skill to 100.

While you're at it... someone suggested in another thread that using a Flame Atronach actually raises your Conjuration and Destruction because of it's Firebolts. Any idea if this is true? It wouldn't be the first Perk/Spell from one School that had an effect on another.

I doubt a Flame Atronach's firebolts would raise your Destruction skill because it is the one casting the spell, unlike the Bound [Weapon] spells where you are basically using Archery, One-Handed, or Two-Handed.