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this is for in-game purposes

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Best Natures are not set in stone, but since you mentioned ORAS instead of gen6 I assume you mean in-game instead of competitive.

I'd personally look for an Impish mightyena if you have the ability Intimidate. Since Mightyena doesn't use Special Attacks often it is good for taking a physical beating while not losing out on much.

If you have Quick Feet for an ability then you will want the Adamant Nature (please put Facade on this Mightyena. It just makes it that much stronger when poisoned or paralyzed). Again, lowering Special Attack, but raising the actual attack stat. Mightyena will outspeed most of the competition with this ability when it suffers so it is going to be a very fun ride!

and if you luckily have Moxie then go with the Jolly nature. If you haven't caught the drift yet, this one lowers special attack as well. It raises the Speed Stat and lets Mightyena outspeed some other Pokemon. A single Pokemon down from there makes Mightyena into an unstoppable force for the remainder of the battle.

Source: I looked up the Impish nature on this server, and the other 2 natures I memorized by heart. I looked up http://pokemondb.net/pokedex/mightyena for the abilities. Now I'm not saying that those natures are the BEST but I'm saying that they're probably and most likely BY FAR THE BEST FOR MIGHTYENA.

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The simple fact is that there is no "best" Nature for any Pokemon. But there are better Natures, depending on the Pokemon and how you intend to use it. The first step is to look at the Pokemon's stat distribution of that Pokemon.

For Mightyena, we can see that it's physical Attack is it's highest stat. This is followed by it's Health, Defense, and Speed. These things indicate that Mightyena is probably best suited to more of a brawling role, giving and taking physical attacks.

This is further indicated by looking at it's movepool. Mightyena naturally has access to strong physical moves like Crunch and Sucker Punch, as well as good utility in the form of Taunt to block set-up moves from the opponent. It can also be bred with good coverage moves, dealing Super Effective damage to Pokemon types that would be Super Effective against it, like Poison Fang for Fairies and Bugs, as well as Play Rough for Fighting.

Looking at all these things together, we want a Nature that benefits Mightyena's physical Attack, or it's Speed. Depending on how you intend to use your Mightyena, a Nature increasing Defense to wall out other physical Pokemon. We can also see that Special Attack is not a relevant stat for most Mightyenas, so a Nature that reduces this stat is probably the best choice.

For these reasons, the "better" Natures for Migthyena are Adamant, Impish, or Jolly, depending on how exactly you intend to use the Mightyena.

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The best possible nature for Mightyena probably would be Calm, which ups Special Defense but lowers Attack. This would work well for Mightyena's low Special Defense stat, and reduce its higher Attack stat.

Pokémon Natures | Pokémon Database
Mightyena Pokédex: stats, moves, evolution & locations | Pokémon Database

Lowering Mightyena's Attack stat will make it seem stronger when it is level 100 but if you're getting a mightyena to level 100 you want a pokemon that is actually a strong level 100. Mightyena with decreased attack will not fit the bill for that. Though making a balanced pokemon by covering its weaknesses is recommended I think you'll find that Mightyena likes to keep it's attack stat and the only Special attack that can really make Mightyena suffer is Aura Sphere.
Calm is a terrible Nature for 99.9% of Mightyena. Though if you want to hopelessly raise its Sp. Def, you should probably go with Careful, since it won't lower Mightyena's best stat.