Griffon The Brush Off (S1)/ The Lost Treasure of Griffonstone (S5)
So hard to pick one or the other….Both episodes involve Pinkie Pie and Rainbow Dash dealing with Gilda the Griffon. In Season 1’s Griffon The Brush Off, Pinkie tries to improve Gilda’s attitude with a party, and Rainbow ultimately shows her loyalty to her pony friends when Gilda reveals her nasty attitude. In Season 5’s The Lost Treasure of Griffonstone, Pinkie and Rainbow have their Cutie Map episode that sent them to the Kingdom of Griffonstone, where their friendship problem gets solved by helping Gilda realize that her kingdom does not need a golden statue to be a proud species. Hmm…for this slot, I’m picking the earlier episode because Pinkie and Rainbow share more screentime together.
Other Nominees: Wonderbolts Academy (S3),

Feeling Pinkie Keen (S1)
Even after 5 seasons, I still consider Season 1’s Feeling Pinkie Keen to be the episode with the most focus on Twilight and Pinkie in the spotlight. Simply because this episode had Twilight trying to figure out the Pinkie Sense. The moral may have been poorly misinterpreted, but this episode is the episode that first comes to mind when I think of just Twilight and Pinkie.
Other Nominees: Green Isn’t Your Color (S1), MMMystery on the Friendship Express (S2), Too Many Pinkies (S3), Trade Ya (S4), Party Pooped (S5), The One Where Pinkie Pie Knows (S5)

Putting Your Hoof Down (S2) Note: Unofficially challenged for position by a Season 6 episode.
This episode isn’t bolded because since I can’t find an episode that focuses on these two ponies specifically, I’m settling for an episode where we see the most screen time with these two together. As of the end of Season 5, Pinkie Pie and Rarity had spent the most time together in this episode as the Straight Mares to Fluttershy’s conflict. They both give Fluttershy methods of being less of a doormat, witness the change in Fluttershy’s behavior at Sugarcube Corner, got chewed out by “New” Fluttershy, and are present to Iron Will’s “collect payment” scene where Fluttershy realizes she’s not 100% satisfied with her new self that she refused to pay, leaving Iron Will to learn a new method: “No means No”. Whew! However…before I was able to post this, an early episode from Season 6 aired, and it has Rarity and Pinkie more closely to a starring role. By this point, I’m not “officially” including Season 6 episodes, so I’ll leave this post like this for now.
Other Nominees: None others

Pinkie Apple Pie (S4)/Hearthbreakers (S5)
For a short while, I’d considered Season 4’s Pinkie Apple Pie to be a Pinkie Pie and Applejack-focused episode, but after see Season 5’s Hearthbreakers, I believe the latter is better. In P.A.P, the conflict comes from A.J. wanting her Apple family to get along among each other to give a good first impression. Pinkie didn’t fret over that and was only upset that they didn’t learn for sure that they’re related. However, come Hearthbreakers, the worry and concern does come to both Earth Ponies. Applejack felt Pinkie’s Pie Family would have been happier to do the Apple Family traditions instead of the Pie Family traditions right away. The results were a disaster and at one point, Pinkie cried, “Don’t make me choose!” [between the family she was born into and the friends who love her like one] Heck, both of them shared a crying scene in the caverns. So the verdict: Both of the episodes are excellent candidates, but Hearthbreakers put worry and conflict on both Earth Ponies rather than just one.
Other Nominees: None others

Putting your Hoof Down (S2)/Filli Vanilli (S4)
Noticed how I didn’t bold these episodes? No matter where I look, I can’t find an episode where the focus is on Fluttershy and Pinkie Pie. I did say I’d fill the spot with an episode where the two ponies interact with each other a lot, even if the focus is not on them. Anyway, why I’d chosen Putting Your Hoof Down: Despite it being an episode focusing on Fluttershy taking assertive lessons too far, Pinkie (along with Rarity) acts like the straight mare, giving advice to Fluttershy. As for Filli Vanilli: Throughout this episode, Pinkie keeps insensitively worrying Fluttershy about how everyone would silently criticize her. Until, an episode comes where the focus is definitely on Fluttershy and Pinkie, these two episodes are the runner-ups to this category.
Other Nominees: None others