Honestly I think there should be a new set of mane characters. Now that Twilight is a princess, she has royal duties to attend to, and all her friends have achieved their goals. Rainbow Dash is in Wonderbolts Academy, Rarity has had many fashion successes, Fluttershy has learned to balance being shy and being assertive when necessary, Pinkie Pie is Pinkie Pie to the max, Applejack has already won the competitions she's wanted to win.....
It think it would be a wonderful new story direction to focus on whole new characters entirely, and to take a little more inspiration from the classic MLP, when they went on real epic adventures...Castles, dragons, sea ponies, monsters, magic (minus the humans of course).
My fear is it honing in on the CMC. That would be beating a dead horse. I want them to either get their cutie marks or find out they wont get any at all. They can't be blank flanks forever. It'd also be nice to see Spike aspire to be more than just Twilight's little helper. Will he stay in Ponyville or will he become some sort of royal attendant or something?
And can we treat Princess Luna more like a princess? Can the new main character maybe take tasks from her instead of Princess Celestia? Maybe Twilight can get some training or whatever from Luna? There are so many possibilities, but to be honest I don't want fans to have too much say in the direction of the show. That could end in disaster. I want to see Lauren Faust get back on board. Season 3 was a watered down continuation of the first 2.