Core Theme:

Pacifistic, kind-hearted, and exceptionally brave and intelligent magic-based protagonists whose respective stories would begin when a mentor like figure would appear, stating that they were chosen to embark on a journey to meet new friends, and would face certain hardships, including fighting a red themed multiversal entity, along with a sniveling bratty youngster who craved nothing but power. During this journey, it would be revealed that both had this power, even when they were very young children, and said power would ascend to an even higher level of power, which was caused by another powerful entity. Their respective stories would also have them discover certain places and items, with friendship being an incredibly important part of said stories.

Connections:

Young magical protagonists from decently popular franchises from the 80's, and though they were far from the first protagonists to appear in their respective series, they were by far the most popular of them all when they came around, most notably in the early to mid 2010's (EarthBound being a heavy inspiration for Homestuck & Undertale, which came out in 2009 and 2015, respectively/MLP having a GIANT fandom in the early-mid 2010's (for better or for worse), and being a heavy contributor for the show's success).

Their stories would begin with them having a relatively small (or lack thereof in Twilight's case) amount of friends, until one day, a mentor-like figure (Buzz Buzz/Princess Celestia) appeared, and stated that they, among all else, were chosen to embark on a journey to meet new friends, facing hardships, including defeating a red-themed, multiverse threatening god (Giygas/Tirek), and a sniveling, bratty, borderline psychotic youngster who craved nothing but power (Porky Minch/Cozy Glow).

Their respective “chosen one” statuses would, although contrast heavily (Ness was chosen by Buzz Buzz due to a prophecy that told that he, alongside the rest of the Chosen Four would time travel to another timeline to defeat Giygas/The Elements of Harmony choosing the bearer who has the qualities necessary to be wielded), both have a significant theme of friendship and meeting new people to become who they are.

Alongside this, both would also have to defeat a cult that has a certain emphasis on being the same/similar looks wise (Happy Happyism, and having an association with having almost everything being blue/Cult of Equality, for having each pony’s cutie mark being an equal sign).

Later on, both would ascend to a higher power during their journey (Becoming the actual UNIVERSE/Alicorn form), which was caused by an all powerful entity (Truth of the Universe/Princess Celestia), that would link them into a form of immortality, along with bigger and newer powers as well (Ness with the powers of the universe/Twilight with the magic of alicorns).

Despite their (former) antisociality/quietness, as well as their general appearance, both are portrayed as heroic, kind, pacifistic, and exceptionally brave, and are described as exceptionally intelligent (Poo stating he was impressed that Ness learned PSI as quickly as he did, and Twilight being shown to be incredibly booksmart, even as a child.).

Hell, even as very young children, both had signs of these powers as well (Ness as a baby was able to move his bottle just by pointing at it, and Twilight, as a filly, was a part of Celestia's School for Gifted Unicorns, where she was able to hatch Spike, and become basically his sibling).

Speaking of which, both have animal companions that helped them at the start of their stories, and would give them the boost that they needed to start their journeys, away from their respective homes (King/Spike).

Alongside this, with their team, both were destined to discover new locations/items to help awaken their and their team's power (Sanctuary Locations/Elements of Harmony), and this would allow them to awaken their powers, which involved friendship in a way.

Both also have had crossed over with other franchises from their respective, multi-billionaire companies (Nintendo/Hasbro) to make other beloved pieces of media (Smash Bros/Friendship in Disguise), where they play prominent roles in saving their respective worlds and allies (Ness, along with Dedede, Luigi, Sonic and Kirby saving the universe against Tabuu/The Mane 6 and the Autobots beating the Decepticons and Chrysalis).

Both would also fight someone who encapsulated the concept of their/other's nightmares (Ness's Nightmare/Nightmare Moon (who is now Princess Luna).

Animation Potential:

Twilight can turn one of Ness's bats into a potted plant, as he looks in confusion and slight annoyance.

You can have a more mid-long ranged battle between Ness's PSI and Twilight's spells.

You can also have Ness's bat and Twilight's Staff of Sacanas clash with each other like a semi-lightsaber clash.

Have Twilight counteract Ness's PSI abilities by trying to reflect it onto him, but Ness absorbs it with PSI Magnet.

You can also have a wholesome moment where they talk about the adventures they had with their friends, and as a result gain more and more respect for one another.

You can also a potential beam struggle with Ness's PK Rockin Omega and Twilight's fuckoff laser she did against Tirek.

You can also just have them flying around and shooting Magic and PSI with each other, with some of Ness's other ranged shit like his slingshot and yo-yo coming into play.

You can also have Twilight try to seal Ness's PSI, only for it to backfire since PSI technically isn't really magic, it's moreso a physical power.

With Twilight's Apples to Oranges spell, you could have a funny moment where one of Ness's bats gets turned into a bouquet of flowers.

You can even have Ness transform into a dragon with the Bag of Dragonite, and go on the more aggressive side, making Twilight to adapt and have her go on the aggressive side as well, and speeding around him as well.

Have Ness's PK Thunder Tackle go through Twilight throwing shit at him, like trees and whatnot.

You can also have Twilight banish him to the moon in order for things to not go out of hand, and Ness teleports back to battle.

Have their forcefields/shields come into play, and try blocking their attacks, only for them to get countered by one of them throwing the other telekinetically.

And at the end, death or not, have them end up as friends, and neither one had any hard feelings for one another, kind of like SpongeBob vs Aquaman. Or have a Ending like Miles vs Deku

Megapost! Ness vs Twilight Sparkle (Unbounded Friendship)