Here I have uploaded my Skyrim INIs[www.nexusmods.com] which I got the best result in performance and graphics. My page on Nexus will be updated more frequently.
If yoou use an AMD graphics card, use the AMD Radeon Adrenalin 20.x driver to continue with your good experiences on the game and graphics and my settings. This version AMD drivers support Windows 10 already. I'm currently using version Adrenalin ReLive 20.1.4.

But keep in mind, that usage of VRAM on Win8 and Win10 is still limited for DX9 games up to 4GB only, not higher as it was possible with Win7.

To be able to use the new VRAM memory feature which came with Win10 Fall Creators Update, you need to disable Autodetect VRAM setting on your enblocal.ini and set the real VRAM size like

[MEMORY]
AutodetectVideoMemorySize=false
VideoMemorySizeMb=5232

With my settings on Ultra you get up to 62 FPS and usually an average of 45 to 58 FPS, almost more than the mandatory 30 FPS to experience smooth scripting. Even my Low settings let you experiencing up to 60 FPS and so a smooth scripting execution.

But, starting with Windows 10 Version 20H1 the operating system (OS) applies the graphics processor (GPU) to applications. That means, the profile settings from GPU vendors are overwritten. Only if the OS has no GPU settings for an application, GPU vendors settings will be applied.

RecentIy played with about 428 active mods including 242 plugins. Since I use Purity mod, they are much less texture mods now.

My reference hardware is nVidia GTX 1060 with 6GB VRAM and an Intel i7 8750 and 16GB RAM and SSDs only.

Remember to change your graphics reference in the SkyrimPrefs.ini under display section (sD3DDevice=) and your display resolution (iSize H / iSize W). Otherwise the game will overwrite the whole INI. You must also check the language Setting (sLanguage=) in the Skyrim.ini, otherwise the Steam game management will start downloading the languages files for this language.

Mod Organizer and some other mod manager tools like STEP makes and uses its own Skyrim.ini and Skyrimprefs.ini located at Mod Organizer/profiles/your profiles name. So be aware to replace or change the right INIs to get your results.

To manage different INI presets you can use Skyrim INI Manager[www.nexusmods.com]

My recommended graphics mods in install order you can find here
https://www.nexusmods.com/skyrim/mods/edit/?id=51300
watch the mod files on several mod recommendations they provide extra mod for nonENB with similiar effects or patches for nonENB users. I usually use 2k resolution and texture of graphics mods, not more. And read the section about Performance & Stability, I used a lot of the recommended stuff to get the best out of my INI settings. On my download section on Nexus you can also find my own SkyrimPrefs INIs I am using currently.

Instead of the listed mods mentioned above, I currently use only Purity by Laast and the additional landscape and cities textures. It is worth to try it out alternatively.

Additional performance and stability is possible using SKSE 1.7x[skse.silverlock.org] and memory settings[www.nexusmods.com] on skse.ini.
It is recommended to use Stable uGridsToLoad Cell Stabilizer[www.nexusmods.com] when you want to change your uGridsToLoad settings without damaging your saved game file. But be aware that if you save a game after you have altered this value, the new value will be incorporated into your saved game. This is worth noting because the game only allows you to load a saved game which has an equal or lower uGridsToLoad value than your current value; you will not be able to open a saved game with a higher uGridsToLoad value in your INI. This means if you lower your uGridsToLoad value again, you won't be able to load up the saves which used the higher value. My older INIs contain settings for uGridsToLoad=7, if you want to use lower value, you will ease the scripting engine, as scripts are not starting so early as with higher values too. This setting is known to have impact on performance regarding scripting, that is why I could level this by higher values for fUpdateBudgetMS.
But with my newest settings since version 1.9 you don't need a high uGridsToLoad setting. Compare on your own and make a screenshot with a lot of far distance objects, close the game, open Skyrim.ini under [General] section change uGridsToLoad=5 and uExterior Cell Buffer=36, save the INI, start your last savegame, make again the same screenshot, and close your game, and compare both pics. If you like it, you can stay with this settings, but consider what I said a few lines before.
Only with Stable uGridsToLoad Cell Stabilizer[www.nexusmods.com] enabled you can switch uGridsToLod back and forth without damaging your savegame. But keep watching on orphaned scripts with Save game script cleaner[www.nexusmods.com] before and after every switch. And use FPS Counter[www.nexusmods.com] , or use the newest Steam Client and enable the integrated FPS counter, to make savegames at close to 60 FPS, sometimes you have to turn around and find a view to get this FPS. This makes sure you get the closest best performance when loading the savegame again on other uGridsToLoad settings. Best to be done in Cities or Houses.

If you don't use mods with a lot of scripting or none or only one follower, you should set the Papyrus setting in Skyrim.ini to default

[Papyrus]
fUpdateBudgetMS=1.2
fExtraTaskletBudgetMS=1.2

Except the Skyrim Project Optimization, I used nearly all of the recommendations from Skyrim Stability Guide[www.nexusmods.com] and Skyrim Graphics Guide[www.nexusmods.com]

Additionally I used ENBoost[wiki.step-project.com] only to improve memory management for a better graphics experience. If you want to use it, read careful which files you need and what you need to configure in the enblocal.ini, to get the best experience on your graphics. There is no need to change anything on my INI presets provided here. If you start the game now, on the loading screen you will see a red line saying: PATCH SPEEDHACK ENBoost turned on in enblocal.ini, graphics modification disabled.
And load order from LOOT[loot.github.io].

You have to travel a while through Skyrim until you get all advantages and all texture well loaded from your new settings.

If you want to use ENB presets, use Rudy ENB, RealVision or AIR ENB.
Just change the settings on this INIs according modders recommendation in regards of

[Display]
bFloatPointRenderTarget=1
bTreesReceiveShadows=1
bDrawLandShadows=1
bShadowsOnGrass=1
iMultiSample=0
bFXAAEnabled=0
iMaxAnisotropy=1

And make sure you edit the right INIs, when you are using a mod manager.