The first Dune game was pretty unique mix of adventure and strategy.

Sword of the Samurai is an old management strategy game with couple action elements and smaller battle strategy system. But it could be argued that the three smaller parts of the game are just minigames. An exceptional game nevertheless.

Palworld.

The fact that this classic is not yet in the Top of OP's first list makes this thread almost unbearable to me.

I'll update, on second glance it does fit the criteria. 

The first Dune game. It mixes Adventure, economic sim, some light RPG elements (your main character gets some new abilities due to his proximity to spice and drinking the water of life) plus strategy to fight the Harkonnen and the Sardaukar off Dune.

Black & White is a city builder mixed with Adventure, Pet-raising sim and some RPG elements.

The TNO mod for Hearts of Iron IV turns the Grand Strategy game into a giant CYOA (Choose your own adventure) style of game and with a much deeper economic simulation yet still has some Grand Strategy parts.

Graveyard Keeper is an Adventure, an RPG, a building game and an economic simulation all rolled into one.

Metroid Prime-
A mixture of metroidvania and a mystery game because of it's scanning mechanic. It's also 3D unlike other metroidvania games which make more emphasis on open world (or pseudo-openworld). The metroidvania genre is automatically genre-bending in it's nature as Metroid is a wild combination of Mystery, Shooter, Puzzle, Platformer, Openworld (pseudo-openworld) & Adventure. Same goes for other metroidvania games, it's just Metroid Prime is different as it's 3D with a scanning mechanic which allows for more mystery & openworldness.

Super Smash Bros-
Brawler, Fighting, battle-arena, online-battle-arena (OBA) & Platformer.
It's definitely not your typical fighting or brawler game thanks to it's platforming mechanic. This is what makes it so different.

Yep, that counts. It done Neir Automata before Neir automata. That game was epic. 

Kirby-
A combination of a platformer & porn simulation game:
Kirby is all pink and likes to show off skin. Then naked Kirby uses oral to copy other enemies' abilities. When he sucks enemies in, every part of them goes into his mouth, every part. He can blow & suck too XD. In Kirby and the Forgotten Lands, he can even turn into a traffic cone to penetrate his enemies, he usually turns into spikes to do this so this new mechanic puts emphasis on the 'type' of penetration. After having a wild time he becomes out of breath and needs to recover by eating foods, creating a simulation mechanic (Porn Simulation).

P.S - I hope no one takes me seriously. I trust you guys XD.

Deffinitely :D. I loved Nier Automata too :)

I am going to go out and say the biggest genre bending game that I played was mass effect 2. Because it goes from rpg to third person shooter to best story rpg etc.