I'd like to hear about any work(s), with a main (or at least very significant) character that is a misanthrope, who pretty much distrusts everyone. (perhaps being okay with animals and small children [whose flaws are only natural, from whom more cannot be expected ...and who cannot yet have developed the depths of bad behaviour, that so many adults have in spades], but pretty much no one else)Preferably due to betrayal.Preferably betrayal by people he/she had liked, trusted, and respected, especially much. z91f

Aside from Tate no Yuusha, which I already know about.
(and Naofumi does rather soften relatively early. After the bit where... To avoid spoilers: after that thing happens that, as a side-note, restores his ability to taste food)

A pretty deep work could be Kore wa Koi no Hanashi.

From the description, it would appear that those works involve people who are lacking in emotion/desire and ability to socialize or connect with people. Having some kind of social anxiety, or other.
In the case of Sekine-kun no Koi, there might also be a lack of interest in having social ? (i.e. asociality/non-sociality. Not to be confused with anti-sociality ...neither of which, should be confused with misanthropy. All can lead to limited socializing, but for completely different reasons and in completely different ways)

Either way, none of that is misanthropic.
No strong distrust of everyone.
...
Well, I'll grant you that they sound, from the descriptions, deep and interesting.
I'll put Sekine-kun in my wishlist (we'll see if/when I get around to it) ...and give Kore wa Koi no Hanashi a look, as it sparks my interest, for reasons outside of what I am asking for here
...but these are not, at all, what I asked for.

I spotted Kaifuku Jutsushi no Yarinaoshi described as a "revenge series"...
Certainly qualifies according to what I request here, but...

The character becomes a bit too twisted/broken. (by the very severe mistreatment he's is subjected to)
His goals are still kinda good, and the targets of his revenge are all very well deserving of it, but he's quite callous and manipulative towards the innocent, as well. I understand why he almost completely loses any shred of humanity, but that doesn't mean it isn't still terrible.
Also the series has rather too much sexual "fanservice". A lot of it involving rape. The rest of it is quite gratuitous and obnoxious (I can tolerate it, but it's annoying), but the rape stuff... that's rather disturbing. I'd be okay with a lot of the rape, if it wasn't for it being presented as something to be aroused by.

(I'm still reading it, but...)

Handa-kun not really mistrust but he just misunderstands and thinks that everyone hates him.

Chinese Translator Accepting translation requests if the manga interests me!

Quote from SephiriaChronos

Handa-kun not really mistrust but he just misunderstands and thinks that everyone hates him.

Thinking you're hated (and/or distrusted) by everyone, is rather different to hating (and/or distrusting) everyone.
...
How do people manage to not understand this?

I'll quote the lead section of Wikipedia's article on misanthropy (emphasis mine):
"Misanthropy is the general hatred, dislike, distrust or contempt of the human species or human nature. A misanthrope or misanthropist is someone who holds such views or feelings. The word's origin is from the Greek words μῖσος (mīsos, "hatred" and ἄνθρωπος (ānthropos, "man, human". The condition is often confused with asociality."

I cannot, for the life of me, understand why anyone would think that this has anything to do with
being uninterested in social interaction or in people, being shy or socially inept/incompetent, being hated/disliked/shunned/ostracised/bullied by others, or anything like that
...or necessarily have anything to do with not interacting with others.
How does any of that, have anything (in any way, shape, or form) to do with hating/distrusting everyone?
(granted, being hated by other, may eventually lead you to start thinking that everyone is scum, but...)

Granted, on the not interacting with others, misanthropes tend not to do so, that much.
After all, it is generally regarded as unpleasant, to interact with people you hate, despise, and/or deeply distrust
...and if you think that essentially all humans are hateful/despicable/untrustworthy...

But such limited social interactions is NOT because they don't have the social skills, or lack any interest or desire to have social s, friends, or a girlfriend/boyfriend, or anything like that. (they might lack one or more of those. They might not. They might indeed have great social skills and a great desire for friends and a romantic partner)
Rather it is simply because there is pretty much no one whom they don't hate/despise, and therefore essentially no one they'd wouldn't hate interacting with, much less be able to befriend.
(with the possible exception of animals, maybe children ...and possibly a rare few individuals, they've found to be more-or-less acceptable/tolerable)

I pray that makes things clear...

Well if you liked tate no yuusha and wanted something a bit darker you could look into
Dungeon Seeker.

If you want your misanthrope to be cruel as well you could look into
Wortenia Senki

Quote from lesterf1020

and wanted something a bit darker

Yeah darker, but most importantly I want the misanthrope to stay distrustful for longer, or permanently. It should take a lot (and a long time. At least a couple of years, I'd say), for anyone to be able to get their trust.
They might be able to trust that they'll do a certain job, a lot easier (but still not nearly as easily as with a normal person), but proper trust...

If you want your misanthrope to be cruel as well

Nah, not cruel. Or, well, rather harsh perhaps, and hungry for revenge against those who wrong him/her (or who are evil and unfair, generally), but not straight out cruel or evil, as in the previously mentioned Kaifuku Jutsushi no Yarinaoshi.
On the contrary, I'd like it if they have strong moral principles ...only further fuelling their disdain for their fellow man. (and if their hate fuelled harsh actions are actually a bit too rough, compared to what their principles say they should be... that'd be fine)

Most important is a deep distrust and disdain of everyone.
Preferably due to having been betrayed, preferably by ones they had trusted. (and if the people they trusted and knew the most, turned out to be such atrocious scum who were never really their friends/whatever, why should they expect other people to be any better? Hence a deep distrust of everyone, except maybe animal and/or children)

Seeing if Arifureta Shokugyou de Sekai Saikyou qualifies was a little hard to tell from the description here. I tried checking the description on Wikipedia, which seems to indicate at least a strong level of cynicism, so it sounds worth checking out.
The descriptions of Dungeon Seeker and Nidome no Yuusha wa Fukushuu no Michi wo Warai Ayumu... Yeah, those sound like they certainly qualify.
What limited descriptions I can see of Wortenia Senki, however, are rather unclear on the issue...

Thanks for the tips : )
That seems to be a bunch of good, relevant, suggestions.

P.S. It would be nice with some stuff that isn't isekai, mind you. I find this recent flood of isekai stuff, to be a bit annoying. Not that some of them aren't great series, mind you, but it's a bit much with this massive amount. Not everything has to be isekai. (and all the skills and levels, as if it were a game, is something I find rather absurd and annoying)

I see that Misantrope and Misantropy actually exist as categories, here (having those as two separate categories, seems like a terrible idea...)

...but which are clearly not properly applied.
They aren't applied to Tate no Yuusha, Kaifuku Jutsushi no Yarinaoshi, or any of lesterf1020's suggestions
...but they are applied to series that appear to just be about unsocial/asocial characters (including the seemingly rather ironically named Misanthrope na Kanojo, that by the description, seems to not involve the slightest bit of misanthropy. Just a mangaka who doesn't understand what the term means)

Though I also found Bocchi Tenseiki (Novel), where the description starts with "I DON’T TRUST ANY HUMAN BEING.".
Yeah, that's clearly misanthropic.

If you are going to use the categories to search you should probably stick to betrayal and revenge. Those categories tend to have the bulk of misanthropes.

If you want something dark and messed up you could try Sekai Oni. At least one of the main characters is a misanthrope. It is not immediately obvious because for plot reasons they don't interact with a lot of people in the beginning.

Quote from lesterf1020

If you are going to use the categories to search you should probably stick to betrayal and revenge.

Yeah. Most of the series in those, have characters that don't so much hate everyone, so much as particular people/groups, but they're a far better bet than the actual misanthrope-categories, rather ironically. (which have only a handful of series, almost none of which involve misanthropy)

BTW, having just gone through Dungeon Seeker, I'd wouldn't say he's quite a misanthrope IMO, actually (kinda misanthrope-ish, but...), and even aside from that, I found it somehow a little underwhelming, for reasons I can't put my finger on.
Still it did kinda "scratch my itch", so to speak.

Besides, series with misanthropic protagonists are uncommon (for many, and very understandable, reasons), so I appreciate anything at all decent, I can get my hands on. (though I'll probably not be going through the other potential series I hear about or find, as quickly as I did with Dungeon Seeker. I don't usually just speed through, without any pause or anything)