2 punches only

Maud Pie and One Punch Man

He's a hero for fun, she likes rocks. He's bored with no challenges, she's bored even with a challenge. He's a human who's never noticed and she's a pony who gets all the attention. He's her father and she's his daughter. Together, they are unstoppable. They are Saitama and Maud Pie

Alchemist Mathematics

Sunburst and Full Metal Alchemist.

The Elric brothers are quite the group. Edward is the headstrong of the bunch, despite being less than average in height (Don't call him small) with a metal arm and leg. Alphonse, despite being the youngest, is the biggest, even if his soul is in a set of armor. And there's Sunburst, the middle child that's easily the brains and is a unicorn... Wait... WHAT!?!?!?

The short but the Brave.

Pipsqueak and One Piece.

The famous treasure in One Piece is a dangerous journey to go in alone. Luckily, Monkey D. Luffee and his brother Pipsqueak are brave (or stupid) enough to go on this adventure and make their crew!!! Anchors away!!!

That makes no sense!!!

Discord and Bo Bo Bo

Hey, you! Yeah! You!!! Name's Bo-bo-bo! You may know me from my Anime series from Toonami, but, we're doing a reboot with enough fan pandering to you Bronies and Pegasisters that enjoy me! But, to make this interesting, I adopted myself some weird kid named Discord, who completely understands me, not unlike my friends. He's not evil; only if he goes bald, but that'll never happen! No way!!!... You're still here? Go!!! Read my adventures!!! Go! Now! Don't make me use my nose hairs on you!

I like the Saitama one from One Punch man... Though it would be curious to see some other ideas too not related to anime.

Example: Lilith and/or Maya from the Borderlands series raising the Dazzlings

5347171 *All sirens annoyed by Sonata's taco*

Pony or human?

5347187 I would think pony. They're originally from Equestria before coming to the Mirror world, so yeah.

Also, another one...
Ruby's Rose:
Ruby Rose raising a young Roseluck.

5347211 you gave me that idea before. But, what about Daisy and Lilly? Those three are synonymous with each other! Unless... FILLY ATTACK!!!
*All three tackle Ruby*

5347283 That would be a good for the saying "Triple Threat"

I so want to read the One Piece and Bo Bo Bo ones!

5347867 you can make them if you want. I'm throwing out many ideas that anyone can use. I personally haven't seen much of either, though I'm more in line with Bo-Bo-Bo... Mostly because of the randomness

5348438 I'd love to, but I don't think I can do it well. Someone's bound to make them though.

5348446 well, I can give some advice. Since you're doing something random... BE RANDOM!!! Add more randomness with Discord and have everything not make sense!!! I can help if you want, though it's gonna involve a lot of binge watching... And finding the transcripts to each episode. (I do that with my DerpyXFuturama fic

5348462 That's actually another problem. I'm not gonna have time to binge watch, I'm starting a new job as a truck driver soon. But it's definitely something to put on the to-do list.

5348465 A truck driver!? Sweet! Hopefully, you nickname yourself "Big Mac" or any other stallion name.

5348786 I'm going with my oc, Nova Blaze. Big Mac would be funny, though.