Testing, Testing 1, 2, 3 (S4)
Out of all the episodes so far up through Season 5, this episode has to be my most relatable episode; taking the pony I relate to the most (Twilight). I think the best part was how this episode showed that even though Twilight's now an Alicorn, she still has room for improvement. People complaining about her being too perfect (shakes head with a wry smile). All throughout this episode, Twilight was trying to help Rainbow Dash. If Twilight really was too perfect, the solution would have presented itself on the first try. And also, it was only when Rainbow brought up her Sherlock Scan ability did Twilight have the missing piece of the puzzle of coming up with a study method that works for Rainbow. Finally, there's the fact that it's Twilight who wrote the lesson in the Friendship Journal. "Rainbow Dash finally learned the history of the Wonderbolts, but she's not the only pony who needed a lesson. One way of learning isn't better than another. After all, everypony is unique and individual." This is one of my most favorite episodes for the simple fact of showing Twilight not being as perfect as some say she's become since becoming an Alicorn Princess.
Other Nominees: Read It and Weep (S2), Games Pony Play (S3), Daring Don’t (S4), Rainbow Falls (S4),

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)

Sweet and Elite (S2)
Even though this is more about Rarity, I still consider this to be a Rarity and Twilight episode. One big reason is that it involves Twilight’s birthday and Rarity wanting to make a new dress for her. But spending time with Canterlot’s elite cuts into dress-making time that the dress ended up being simple and plain. Plus, with Rarity jumping between Twilight’s party indoors and the Elite party outdoors, Rarity was worried about letting Twilight down. In the end, Rarity announces to the Canterlot Elite of VIPS that she does come from a simple town like Ponyville and got the approval of one of Canterlot’s most influential unicorns, Fancy Pants. Until a better, more focused episode comes, Sweet and Elite is the episode that makes me think of Twilight and Rarity together.
Other Nominees: None others

Applebuck Season (S1)
It was easy to pick this episode to represent Twilight and Applejack sharing the spotlight. All throughout the episode, as A.J. stubbornly tries to harvest the apples on her own despite getting sleepy and cranky, Twilight keeps coming to her, acting as A.J.’s voice of reason to sallow her pride and accept help.
Other Nominees: None others

Bird in the Hoof (S1)/Hooffields and McColts (S5)
For the longest time, I’d considered Bird in the Hoof to be the episode where Twilight and Fluttershy are the focus of the episode. However, Twilight is only with Fluttershy within the 1st and 3rd acts of the episode. Only now in Season 5’s Hoofields and McColts do they stick together throughout the entire episode.
Other Nominees: Keep Calm and Flutter On (S3),