So let's say we want to cut down the cast size a bit, but lose as little as possible of the variety of different characters on offer. Or let's just call it a thought experiment. These are some possibilities, but feel free to post others - and not just for the Manes!

Twilight + Applejack - a farm mare who was chosen as the Princess's student (or just left for higher education) and now returns to her old home forever changed. Smart, sensible and a great leader, but it can kind of go to her head sometimes.
Twilight + Pinkie - an "enjoyologist" who spends her time constantly engaged in "fun experiments" (parties) in order to create a Grand Theory of how to make ponies happy. Also an inventor of of various weird but amazing technology on the side.
Twilight + Rainbow - a girl who laughs at the distinction of jock and nerd, excelling at both academics and athletics. Downside is that (and her ego) don't leave much room for friends...
Twilight + Fluttershy - a total shut-in naturalist, if you can call somepony who spends most of her time outdoors a shut-in). Has published several amazingly insightful zoological papers under a false name, but probably sees other ponies no more than once a month.
Twilight + Rarity - A student of the Princess who looks the part, being deeply connected in the Canterlot life with several eligible stallions vying for her hand. Some might even forget that she's more than just a pretty face - until they checked her grades.

Applejack + Pinkie Pie - The face of Ponyville, who uses all kind of tricks to make her day's work fun. She can do just about anything with apples.
Applejack + Rainbow Dash - An athlete who reaches the top of the field by hard work, dedication, and the support of her family. Her victory speeches always see her thanking them (and plugging their farm) while playing down her own accomplishments... but in a way that almost sounds like bragging.
Applejack + Fluttershy - A strong and nurturing mother figure, she works closely with her animal friends to farm the land. She doesn't mix that much with other ponies, but has a strong soft spot for foals.
Applejack + Rarity - a designer who believes in the marriage of form and function, turning out beautiful and practical garments at affordable prices. (And speaking of marriage, she's looking - but be warned, she won't settle for anypony who works less hard then she does.)

Pinkie Pie + Rainbow Dash - The fastest pony alive, who doesn't race competitively because "it's not fun" but instead puts it to use as a messenger. When she finds a "meanie" bothering others, though, she can't resist taking a break from her work to humiliate them with her flashy, ridiculous abilities.
Pinkie Pie + Fluttershy - A mare with two speeds - one and ONE HUNDRED! She can switch between them pretty unpredictably, too - but she's always very nice.
Pinkie Pie + Rarity - A lavish and unconventional event planner whose unique style has all of society ablaze! But to her, even a young mule's birthday party is as important as the Grand Galloping Gala.

Rainbow Dash + Fluttershy - An amazing flyer who hides her skill so as not to receive unwanted attention. Friend to all the birds of the air. She's outwardly agreeable, but can hide contemptuous thoughts...
Rainbow Dash + Rarity - the ultimate sportswear designer who live-tests all her own work. Believes that there's nothing more beautiful than a body pushed to it's limits. Actually a serious romantic, but comes off as too boyish for anyone to think so...

Fluttershy + Rarity - A secret designer whose name and face are unknown to anyone. All her work incorporates animal themes, and it's rumoured she has animals help make them as well...

7393261
That makes me think of that Amalgam crap. And yes, there is a reason I call it crap.

Combining stuff doesn't always mean you make it twice better.

7393264
Well, the trick is how.

7393261
I like that idea for a story

7393261
I am torn with using VA based merge, or place of origins
I.e, AJ and RD, Flutters and Pinkie, and Twilight and Rares
or AJ and Rares, RD and Flutters and Twilight and Pinkie...

7393261
I think I see the most synergy in Twilight/Rarity, Pinkie/Rainbow and Applejack/Fluttershy. There's something to be added about past generation ponies, like Sparkler, Surprise and Posey that would work for names. Though, it would also require each of them to fill an specific role in the ego/superego/id dynamic, due to only having one possible combination. Most Probably Twilight/Rarity as the ego, Applejack/Fluttershy as the superego and Pinkie/Rainbow as the id.

Overall, I like the concept and I can see it working.

P.S.: Yes, it is kinda like Amalgam Comics, but I see it as a positive thing. Different tastes and all:

7393261 Well, I'm not sure how many other combinations might be possible. But if we combined Twilight and Starlight you'd be doubling up on their strengths and flaws. A pony with insane magical powers, greater than even her mentor, Princess Celestia. Unfortunately, this pony doesn't share her mentor's view of friendship, her world view has become warped. She views friendship as nothing but a distraction in pursuit of power. She's good at masking her distaste for it but deep down she resents her mentor for it and dreams of taking over, imposing her world view on everyone.

7393896
I'm not sure the world could survive such a combination - or Starlight + Pinkie, for that matter.

7394015 I think Pinkie's positive attitude and desire to see the good in others would outweigh some of the more negative aspects of Starlight's personality. She might even be clever enough not to reveal her crazy powers except to those she trusted.

7393261
...this thread is less than six months old, and mine, but I don't remember making it at all. I mean, it's totally the sort of thing I would, but still... normally this would mean someone was probably drunk when they posted it, but I don't drink. Am I going senile at 31?!