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"War. War never changes. Those talking pastel-colored ponies, however... they're new."
I shouldn't have to say this, but seriously: do NOT hold a gun with your mouth. No good can come from it.
I would make a joke about being a grown man who is a fan of My Little Pony: Friendship is Magic, but I think half the internet (including myself) have done that already, so let's move on.
I was given Fallout: New Vegas and discovered the new MLP show around the same time, and while playing FO:NV with all of it's western themes, I found myself picturing Applejack as the courier.
The downed ponies are meant to be feral ghouls. I played fast and loose with their color scheme, however, for added contrast with the Mojave wasteland. That pony in the back is a Nightkin. Their cutie marks are the symbol for radioactive and a crescent moon with stars, respectively.
The gun Applejack is holding (in such a fashion that nobody should ever mimic) is the Lucky .357 magnum revolver. I chose it for its western appearance and distinct look, but I later realized it was even more appropriate that I thought given that the gun basically has its own cutie mark.
That said, I have no idea how she fires the darn thing.
EDIT: Some corrections, anti-aliased high-res version.