Although it technically isn't explicitly about trans people, Terry Pratchett's Monstrous Regiment explores a lot of ground about repressive gender roles and norms, feminism and the arbitrariness of religious doctrine. It does all of this while being absolutely hilarious and a joy to read.

It's also technically part of a series, but like all Discworld books can absolutely be read as a standalone book.

Maybe not an absolute top pick due to not cleanly hitting all your requirements, but I'd still recommend it.

Him by Geoff Ryman. It's an alternate history story where Jesus is a Trans man.

The Seep by Chana Porter is a beautiful piece of weird sci-fi.

Model Home by Rivers Solomon. Haunted house story

Recently read the convergence trilogy and one of the main characters is trans. I liked the books.

Additionally the left hand of darkness is about a planet full of genderless people that change to male/female idk if that is considered trans. The book in general is commentary on gender norms in our society. This one I think puts the most emphasis on gender of the three.

And finally one of the main characters in Robin Hobb's Realm of the elderlings series is also trans or non-binary I think. It is a great depiction of how the actions of a person are more important than their gender, but it is not the main point of the series. Still a great fantasy series I think.

P. S. Everything from Le Guin is great and I highly recommend it.

Haven't read it myself yet, but I've heard a lot of good things about One of the Boys by Victoria Zeller.

Check out Margaret Killjoy. She has written some stories. I only ever read "We Won't Be Here Tomorrow, and other short stories"

I don't think the character in her short story was trans, but it wouldn't surprise me if one of her stories are.

https://en.wikipedia.org/wiki/Margaret_Killjoy

Happened upon it via someone else here, check out Woodworking by Emily St. James

A while ago we read Pet by Awaeke Emezi in our solarpunk bookclub. The protagonist is a young trans girl. Though the book doesn't make it a big thing. Its more about finding a human monster (meaning abuser). It's a really good read and rather short (like 130 pages).

These are mostly binary trans women recommendations, and most of these are by trans authors. If for some reason you want comic book or manga recommendations, I've got those too if you need them. There was also an LGBT spreadsheet in one of the reddit subs for books (either bookrecommendations or maybe fantasy) with a massive list of books, though no indication of their quality.

From the more comprehensive list below, I would recommend:

General Literary Pick: Disappoint Me - Nicola Dinan
General Romance: Chef's Choice - TJ Alexander

Solo Books

Disappoint Me - Nicola Dinan
Great story, often humorous in my opinion. Deals with many aspects of being trans that I think most cis people with little experience with trans people would think about.

Light from Uncommon Stars - Ryka Aoki
This one's pretty well loved. A woman who made a deal with the devil romancing an alien while training an up and coming trans woman who wants to become a famous musician.

A Lady for a Duke - Alexis Hall
Victorian Romance. Does glaze over some of the practicalities of being trans in that era, but I don't think that's an issue. It's okay to allow for a little suspension of disbelief. The romance is pretty great imo.

Pack of Her Own - Elena Abbott
Werewolf. If you like supernatural romance, just read this. Trust me. Sapphic.

Chef's Choice - TJ Alexander
T4T romance with a binary trans man and woman. One of my favorite trans romances I've read. Also, unlike the others on this list, you get a trans man's perspective too. Plus, it's trans experiences from those who are more and less privileged, changing the way they interact with the world.

Orlando - Virgina Woolf
But you probably already know about this one. I'm sure someone will probably get angry at me for including this as trans, but that is what Orlando functionally is in the story, regardless of whether that's how it's meant to be read. It's certainly an exploration of gender of the time, at the very least.

Young Adult (YA) - Fawn's Blood - Hal Schrieve
Vampires. Certainly playing on the idea of a twisted version of Buffy the Vampire Slayer. If you all enjoy YA and supernatural stuff, give it a read. It has various trans characters as part of its cast.

Solo books with trans main characters but don't heavily focus on the trans part

YA - This Delicious Death - Kayla Cottingham
Zombies/Ghouls. People who eat human flesh, basically. Sapphic.

Two Book Series

YA - Dreadnaught Duology - April Daniels
Trans woman superhero main character. Various rep, plus it's Sapphic.

Stealing Thunder Duology - Alina Boyden
First book is very rough and stereotypical imo. The second book is actually pretty fun though.

Trilogies

Her Majesty's Royal Coven - Juno Dawson
One of the main characters is trans, though you won't get her perspective until the second book. I wouldn't recommend reading this specifically for the trans aspect. Also chock full of pop culture references (not necessarily in a good way) even I didn't always pick up on, which is saying something. Overall enjoyable though.

Solo books with trans protagonists that I would not recommend

People Collide - Isle McElroy
Either I didn't get it, or I didn't like it. Some reviews seem to insist this book is great. I personally hated it.

Podcast

This Queer Book Saved My Life - Tons of queer book recommendations.

She Who Became The Sun by Shelley Parker-Chan. It is the first book in a duology, so might not work for you.

If you're okay with a graphic novel, I recommend Nimona: https://en.wikipedia.org/wiki/Nimona

Also has an animated movie adaptation.

Most Ardently by Gabe Cole Novoa. It's a retelling of Pride and Prejudice, with the twist that Elizabeth Bennet is actually a trans boy. Written by a transmasc author, too!

@OmegaMouse I recently read Smile As They Bow by Nu Nu Yi. It’s a Burmese book which features a trans protagonist. Really interesting read and great insight into Burmese culture too.