Oh that's a really interesting question.

I'd say Ico and Shadow of the Colossus, unless you want to group those together with The Last Guardian as spiritual sequels.

salt'n sanctuary

Vagrant Story
Demons Souls
Bloodborne
Bully
Einhänder
Lost Odyssey
Cave Story
Ico
Shadows of the Colossus
Catherine
The Wolf Among Us

Jet Force Gemini for me. Really underutilized potential in that IP.

Enslaved: Odyssey into the West

Ninja Theory is a dope developer. Great freakin game.

Vagrant Story.
Mischief Makers.
Bloodborne.
Shadow of the Colossus.
Diddy Kong Racing
LOD
Skies of Arcadia
And of course, the poster child of this topic: Super Mario RPG: The Legend of the Seven Stars

The Legend of Dragoon
Lost Odyssey
Shadow of the Colossus (If it counts)
Bloodborne
Blast Corps
Enslaved: Odyssey to the West

Some of this is subjective, just because I see people mentioning a bunch of games that I would consider spinoffs.  Doesn't really matter though. Here are my picks:

Undertale
Adventure
H.E.R.O
Anteater
Dead Cells
Duck Hunt
Hogan's Alley
Astroboy: The Omega Factor
Celeste
Wargroove
Untitled Goose Game

That's mostly it.  Even the games I could mention that are obscure to most would still be a sequel or spinoff (or later had a sequel or spinoff).  The video game industry is full of them.

Child of Light

(good call on eternal darkness.  I was going to mention Shadowman, but found that there was a sequel on the ps2 only.  Shame)