I actually managed to soft lock a side quest in The Witcher 3 recently. If you loot a container right as a cutscene begins, the item will be removed from the container but not put into your inventory.

I managed to do this with a key (by mistake) and almost lost around 25 hours of gameplay lol.

In cave story, there is a decision around the middle of the game. If you make the wrong decision you can’t upgrade to the best weapon in the game.

I forget all the details, but i was annoyed when I found out about it.

While playing Final Fantasy X the first time, I got to Old Zanarkand and inside the dome, I saved behind a sealed door in the Cloister of Trials. I wasn't savvy to good saving practices and after solving the puzzle, got into a battle I was completely hopeless to defeat. There was no way to walk back out the door from which I entered, the only way out was through; and with my existing inventory, spells, charged up aeons, etc. I absolutely could not defeat the boss.

It was pretty crushing because this moment is so close to the end of the game, but I gave up and had to come back months (years?) later to fully start the game over. I think maybe I played 99+ hours of Final Fantasy VII and then decided to give X another try. The second time, I was much smarter with maintaining multiple save games for safety. Not to be bested again, I grinded up all of my limit breaks and aeons for safety and completely obliterated the boss in one go the next time around.

I almost softlocked myself in The Evil Within (the first one). I've used up most of my ammo before walking into a boss fight and I just barely managed to beat him by using everything I had. It does give you ammo before the fight but it isn't enough to win, I imagine it would be easy to softlock there. I remember spending a huge time making sure all my shots land so I don't restart.

There are a LOT of these, especially from the 8/16/32 bit era.

https://tvtropes.org/pmwiki/pmwiki.php/Main/UnintentionallyUnwinnable

Takeshi’s challenge I think it was called. Notoriously bullshit game on the famicon

Metro.

All 3 games require you do/don't kill certain people at different levels in order to get the 'true ending'. When I first played I just killed anything that moved, but then found out the consequences of doing so. Honestly it improved my game experience so much more when I had to carefully consider each action.

XCOM: Terror from the Deep had some notorious research tree issues

I played Earthbound as a kid and got stuck in a golem without the item needed to get out. Since I got it used I didn't have the game guide. No idea how much stuff I missed but I never picked it up again.

I'm sure others have mentioned it here, but..

Chrono Trigger.