Gaming

The Longest Journey, 1999.

Don't see it mentioned yet, it's an older game but Remember Me is pretty good

Trying to find some that haven't been talked about yet:

Echo. It's a fantastic experimental infiltration game with an AI that adapts to your way of playing. The setup is very impressive.

Pathologic: one of the three playable characters (the Changeling). It's a bizarre russian game, with an unique world, and messy gameplay. Can't recommend it enough.

Va11 Hall-A: chill bartending game in a cyberpunk setup.

The Blackwell series: comfy, kind of amateurish point and clicks by Wadjet Eye. I like them very much.

Transistor: weirdest game by Supergiant. You play as a redhead with a talking sword. I don't remember much about it except that it was good.

The Fall: (pushing it a little bit, since the protagonist is an AI, but I've always seen here as female.) Criminally underrated puzzle games, disguised as metroidvanias.

Eliza (by Zachtronics): the only visual novel I enjoyed. It's hard to explain, it's about AI, burnout, whether tech dehumanizes people, and solitaire.

Hedon Duology: for something completely different, it's a slightly kinky retroshooter, with amazon Orcs fighting demons.
It may sound a bit dumb, but it's excellent. Huge levels, interesting worldbuilding, and a gameplay based on exploration, puzzles as well as shooting.

There's probably a ton more, but that's all I can think about at the moment.

Plague Tale:Innocence and Requiem

The Last of Us: Part II !

A group of developers have created a version of the game and it's sequels that runs on modern machines: http://nolfrevival.tk/

Edit: this was meant as a reply to @KIM_JONG_JUICEBOX 's comment. No One Lives Forever is a whip smart spy FPS that nails the Bond aesthetic but stars an unforgettable female protagonist, Kate Archer. Download it for free above.

Whoa whoa whats wrong with Senua?

It Takes Two has a great protagonist

Mirror's Edge is a good one I haven't seen mentioned yet. A bit older by this point but it was a fun one.
Transistor is another great one. The gameplay was fine but the art and sound is incredible.

Aquaria

A very well put together Metroidvania. The map is very fun to explore, good boss fights, great music, and interesting story.

Life is Strange and Life is Strange: Before the Storm are some of my favorites.

Great list from @mint@beehaw.org, just a few more:
Gris is an absolute gem.
The A Plague Tale duology is also up there (with Requiem being my favourite game of all time, so I'm extremely biased, sorry / not sorry :D).

Celeste is a classic. It's a platformer. Really amazing game.

Chorus is a space dogfighting game. It has a great core gameloop but imo it is missing out on side content and story.

It's older, but The Longest Journey is good. Unfortunately, the final game in the series kinda sucks.

While it's an ensemble, most people would agree that the main character of Final Fantasy VI is a woman—they just might disagree about which woman is the lead.

I also liked the first Xenosaga game, but again, it's a series that goes pretty badly downhill.

Can I suggest some great novel games?

**VA-11 HALL-A: Cyberpunk Bartender Action **

• play as a bartender and change outcomes of stories by providing different drinks

Fatal Twelve

• death game, mystery, lesbian couple as main character, one of the best

Night in the Woods is objectively the best game ever made by any measure. Tacoma and Gone Home are amazing too.

I mean I dunno, it depends on what kind of games you like, surely?

This is a very obscure one, but there is a mod for Freespace 2 called Blue Planet: War in Heaven which has an amazingly well written story and female lead.

I really liked the Edna & Harvey games

Assassin's Creed Odyssey female lead is canon, although you have the choice to play the male as well.

I'm having a great time finally getting into What Remains of Edith Finch.

Control is excellent

Not female, but the protagonist of Outer Wilds is nonbinary, as is their entire species.

I enjoyed Uncharted: The Lost Legacy. It's a bit shorter than U4, but still worth playing. I liked Chloe and Nadine together.

Stardew valley is fun

Returnal is a great game if you like roguelite mechanics. Great gameplay, art design, and sound. The haptics on the PS5 are excellent too.

The modern tomb raiders are pretty decent.

The Mass Effect series is still my favorite, you can choose your protagonist to be female and the game will adapt accordingly. Or Dragon Age if you are more into fantasy.