Problem solved!
It was an ergonomics issue all along. I tried a sheepsfoot Benchmade Grip that comes with a thumb hole today. It worked amazingly and it was very intuitive for my thumbs! Didn't miss the hole or have to poke around for it, didn't get stuck half way while opening, etc. Even worked with my other fingers. I also tried a few Spyderco from the Tenacious line back to back with it - still didn't work at all, regardless of if I used the thumb, middle, or index finger flip.
After a few more tries on both, it became very clear to me that it came down to how/where the hole was placed in relation to how my hand grabs/holds the handle and how my thumb fits into it all and is able to move. The hole on the griptilian sat in a slightly different spot and had a different "track" that it followed when opening/closed vs any of the tenacious line (and any other similar Spyderco I've tried recently).
Guess I'll have to try each Spyderco in particular more extensively before I buy (unless I collect eventually... but I don't right now). Somewhat inconvenient but at least the mystery has been solved now.