Friendship Is Betrayal/WMG

There is no mole.
Celestia is simply running a Paranoia Gambit against Twilight. She deliberately raised her to be distrustful, suspicious, and incapable of fully trusting anypony. Once she's completely outlived her usefulness -- or until at least one of her friends has died and rendered the elements useless -- she'll step in and reveal the truth before disposing of her unfaithful student.

Spike is the mole.
As he's under a Geas and bound to Twilight's service, she underestimates him and thinks he's fully under her control. He's not. And he's her direct line of communication with the princess...

Twilight is the mole, and doesn't realize it.
She's a Manchurian Agent. Writing the princess regularly is part of her Brainwashing; she simply doesn't remember all she writes.

Rainbow Dash is the mole.
She lied to Pinkie about Gilda manipulating her; it's Celestia who sent Gilda to Ponyville as an Unwitting Pawn.

Fluttershy is the mole.
Ponies seem to naturally trust her; even the hyper-paranoid Twilight immediately saw her as sweet, innocent and pure, and Pinkie was more motivated to protect her from Gilda than the far more vulnerable Granny Smith. This would make her an ideal agent for Celestia.

As a bonus, she may also be the one who ...

All of the Mane Six are the moles
Celestia is playing them off each other in order to get the maximum impact.

In the end, Twilight will bring about Harmony...
...In the form of an empty, barren world, the result of a Pyrrhic Victory against Celestia.

Celestia was Discorded.
Though she was victorious, he managed to leave a tiny, subtle gift behind... And that was the nail leading to this series. Luna came to suspect something was wrong, leading to her rebellion -- though that doesn't preclude the idea that he might have touched her, as well.

Celestia smashed Discord's statue.
While she did this to ensure he'd never find any way to escape his seal and cause chaos again, this actually spread his influence, as his chaotic spirit has diffused across the land.

One of the Cutie Mark Crusaders will be a Dead Little Sister.
While Apple Bloom was shown during Applejack's introduction, something could happen to her in a later arc, while Sweetie Belle is still unaccounted for. Something happening to Apple Bloom or Sweetie Belle would hit the canonical Applejack/Rarity hard, at least... and while Scootaloo isn't related to one of the main cast, that doesn't mean she couldn't end up a Killed Cutie.

Applejack's arc will involve her learning Rainbow Dash was responsible for her parents' deaths.
They were killed five years ago by 'an exploding rainbow'. Pinkie Pie already knows Dash is responsible for something like that. Once Applejack finds out...

Rainbow didn't cause the deaths of the Apple parents.
It's a Red Herring; something else caused the 'exploding rainbow'. A Zap Apple incident, perhaps? Or Celestia. When in doubt, blame the mule.

Rainbow Dash gained the Sonic Rainboom via a Deal With the Devil.
As a filly, she wasn't a very strong flyer, and was constantly bullied. However, she was given a chance to gain considerable strength and speed, and unleash the power of the Sonic Rainboom... unaware of the full price. When she first unleashed it, it proved deeply devastating. Fluttershy only survived because she was knocked off her seat and fell to earth -- this is also why she distrusts Rainbow, as she witnessed just what sort of carnage she's capable of.
 * This may mean that Dash is also The Mole, as Celestia could be blackmailing her with this information... or it could be the true reason why she was going along with Gilda's plotting, as her old friend threatened to reveal the Awful Truth.

Fluttershy's fall damaged her wings.
As mentioned above, she fell all the way from her seat in the clouds to earth. Unfortunately, her landing left her injured and unable to return home, forced to adapt to life in Ponyville. While she is able to fly short distances now, she's still not as strong a flyer as most other pegasi.

Twilight will succeed in overthrowing Celestia, but the process of doing so will turn her into a villain just as bad if not worse than her mentor.
Its the classic plotline after all; tyrant gets overthrown by idealistic revolutionary, but the bloody manner in which the overthrow occurs corrupts the revolutionary and forces them to do unspeakable things, until eventually they can't tell right from wrong any more. Twilight will set out at first to make an Equestria without Celestias torment, but all she will achieve is the creation of a different tyrant.

Celestia's plot will be her undoing.
Regardless of whether or not she actually has a mole among the bearers or is simply relying on her ability to mislead and intimidate everyone, ultimately, the elements can De-Power her. Eventually, she will push all of them to the point where they feel they have to act -- not to save the world or their "friends", but to save their own skin.

Instead of The Power of Friendship triumphing, therefore, their victory will be based on Betrayal -- betraying Celestia's expectations of them. Betraying their own fears and personal failings, acting out of self-interest and self-preservation.

Twilight will take down Celestia the old fashioned way.
Twilight will be unable to use the elements to defeat Celestia... but she or somepony else will kill off Celestia a mundane way, possibly from an unexpected angle while she gloats over victory.

Concerning Cadance and Shining Armor...
Princess Celestia used Cadance to monitor Twilight before she had an excuse to claim her as an apprentice. Once she was no longer needed in that capacity, Celestia drove a wedge between the two by playing them off each other, constantly and needlessly comparing their progress in regard to one another, sowing seeds of resentment and envy.

As for Shining Armor, Twilight believes that he's blindly loyal to Celestia. (Ironically, he may believe the exact same thing about her, robbing her of another potential ally.) The minor matter of Twilight's magical accident killing their parents also hurt their relationship.

The Elements of Harmony still work because they still embody their Elements -- just in a darker way.
Twilight does place a high value on her Friendship with the others... because she needs them to fulfill her goals. Pinkie Pie finds Laughter even in the most disturbing experiences. Rarity is Generous because that earns her the praise and recognition she feels she deserves.

This darker bent is also why Celestia was able to use them herself in the past. It could also mean they're weaker than in Canon; they're not powered by purer emotions, or at least, purity that isn't rooted in self-interest.

The Elements can realign to others.
Going off the above, if somepony who embodied an Element in a better, 'purer' fashion was exposed to one, they could potentially tap into its power themselves. This will be used to put Twilight in a delicate situation by having somepony appear who could claim one -- perhaps a more innocent filly, like Apple Bloom, Sweetie Belle or Scootaloo...? Or some other citizen of Ponyville...?

Twilight will then have to decide whether this new, potentially stronger host is worth taking a chance on, or if she should stick with the friends she already has. Either way, this'll lead to a big Shoot the Dog moment, where she must prove once again that she can be as ruthless as her mentor when it comes to fulfilling her goals.