Off the top of my head:
- Outer Wilds (an entire solar system is a puzzle stuck in a time loop)
- Hades (a roguelike where dying progresses the story)
- Slay the Spire (a hybrid deckbuilder/roguelike where different runs can produce drastically different gameplay and builds)
- Dead Cells (a hybrid Metroidvania/Roguelike with Diablo-style random weapon/item spawns that force the player to use different strategies with every playthrough)
- Into the Breach (from the guys who made FTL)
- Undertale (a fourth-wall-breaking RPG in which you can talk your way out of any battle, with multiple endings)
- Signs of the Sojourner (a narrative deckbuilding game where your cards represent different types of conversation)
- Her Story (a game all about watching pieces of footage from a deposition about a death... or is it a murder?... and trying to figure out what happened)
- Baba Is You (a puzzle game in which the rules are also objects in the game that can be moved and changed)
- Hypnospace Outlaw (a simulation of an alternate-reality 90's internet)
- The Stanley Parable (a game about following directions, or not following them and irritating the narrator)
- The Beginner's Guide (a narrated tour through the games of another developer, possibly without their approval)
What I was talking about are games like Star Control 2 and Dune 1, where they boldly mixed completely different genres and, in SC2 case, added a very deep lore and managed to feed it to you at the right pace, not overwhelming you with information, and giving it in entertaining way.
For example, I would love some nice space RPG with FTL-like space combat. But they just don't mix genres that way these days.
RimWorld - "sims"