Let's keep calm here...
With the = on the flank:
G4:
Prince Blueblood would probably be unable to navigate the one street in the village without help from others.
The Flower Trio wouldn’t be able to tell dandelions from locoweed, and/or they wouldn’t be able to grow anything but weeds.
Derpy wouldn’t be able to cope with air currents.
Diamond Tiara wouldn’t be able to persuade a red-tailed hawk to go after a mouse.
Songbird Serenade (and presumably a cousin of hers*) would develop tin ears.
G1:
Cherries Jubilee would be completely at sea dealing with cherry trees.
Surpise would be like Pinkie under the spell.
Firefly would crash trying a simple straightforward flight directly from Point A to Point B.
* Sia has a cousin Peter who’s also in the music biz.