Put iOS 10 on my iPhone 6.
The most in-your-face change is that "slide to unlock" is gone - it's been there since the original iPhone (and survived a little minimalism mishap in iOS7) but now it's "press home to open". Long time users may have to retrain their muscle memory.
It does feel like that home button is getting overloaded - click to unlock, or maybe thumbprint to open, long hold for Siri, double click for running app cards, double touch (not click) for reachability, and then good old click to get back to the homescreen.
(There's a "Home Button" Settings menu with a "Rest Finger to Open" that made the navigation when using Touch ID a lot friendlier - having to alternate between click and fingerprint reading kinda stunk. Not sure why it's not the default.)
My favorite change is the new set of keyboard sounds. Rather than having the same click for every key, normal keys, white space/shift, and delete all have different sound effects. The result is a delightful little blurble that gives subconscious feedback about what keys you're hitting, very pleasing in an ASMR kind of way.
I do think iOS settings have gotten out of hand. A few versions ago they added a search box for it, but it's still a hot mess - making it worse, it only search the top level - like, the Calendar app has a "Time Zone Override" feature (more on that later), but you can't find it by searching "Time Zone".
Anyway, I suspect they got rid of "slide to unlock" so that they could make the quick operations easier - the widgets that are to the left and especially getting to the camera. (Wish I could find a setting for what mode the camera starts in, One Second Everyday geeks like me almost always are diving straight to video...)