Inspiration Rune: Inversion
This post didn't get much of a response last time so I figured I might try it again.
TLDR; Other runes that provide adaptive stats and bonus damage will not favor the more abundant stat, creating a hybrid build.
Example #1: Syndra deals mostly magic damage, and when she procs Electrocute it would normally deal additional magic damage. With this rune in her secondary path, it would deal physical damage instead.
Example #2: Ashe builds her standard ADC items. With Inversion in her runes, The Sorcery/Inspiration Trait, Celerity, and Gathering Storm runes would give her bonus AP, making her ultimate deal more damage. Also, Arcane Comet would deal magic damage instead of physical, giving her a better mixture of poke damage.
These may not be the best examples, but I think they show the concept.
Many runes offer adaptive bonuses that change depending on the amount of Attack Damage vs Ability Power, or physical damage vs magic damage the champion has/deals.
It seems like all of these runes tend to go with the dominant trait, which is often a good thing.
What if you didn't want this though?
If you are playing a champion who deals mostly physical damage and your enemy is stacking armor to counter you, .. what if you could deal bonus magic damage instead of more physical damage?
Or if you are playing a champion that benefits from both Attack Damage and Ability Power, but the items you want to build are more AD heavy, but you would really like to have some AP as well?
The Inspiration path is all about bending the rules, so I feel that this would be the perfect place for a rune that inverts the output of other adaptive runes.
The part that I am unsure of is if this should be a keystone or not.
As a keystone it could afford some added benefit because it limits the availability of other keystones, many of which would be the main source of the adaptive utility. Perhaps it could even increase the output of these adaptive stats by something like 20%.
As a non-keystone, I think it would be pretty simple, and it would make for some interesting combinations.