Is there any reason NOT to activate v-sync? 'Cause if I don't, my graphics always card nearly overheats trying to reach impossible FPS rates.

I've read many differing arguments for and against, but most deal with setups well beyond where mine is currently.

Graphics to max settings, V-Sync On, turn off nausea creating effects (DoF, Head Bob, etc).
Audio, Subtitles on, Voice to Max, Music to 60-70%, Sound Effects to ~85%.
Input, I use EDSF for movement and A/Z for jump/crouch, so I need to reset bindings for every game.
Gameplay, enable most difficult settings, turn off autorun.

Usually full-screen native res (some games start as a borderless window for some reason), Bloom gets turned off immediately, Vsync off by default but gets turned on if there's screen tearing. Motion blur off, shadows medium, AA at 2X at the most unless it's an older game, Anisotropic to 8X at most, and most other fancy schmancy settings get like SSAO and DoF get turned off. If I'm having problems with FPS being inconsistent between 40 and 60, I use RTSS to cap it to where it'll be stable. If it's uncapped, I use either RTSS or Vsync to rein it in.

your even better of with putting your card in its full power mode instead of optimal then not go with vsync

Alt-Tab, multiple monitors, keyboard media keys, etc... it all depends on the game.
Don't assume that other people share your pet peeve (power usage) when they talk about V-Sync.

Subtitles are a big thing. If theres a lot of 'reduced damage' settings I'll put it to normal, and abuse the save system.

Since I'm left handed, I usually rebind the keys If I'm not playing with controller. I use OKLÇ or PLÇ^ (Brazilian keyboard) instead of WASD.

Motion Blur, Depth Of Field, Chromatic Aberration and Film grain OFF.

I just call it a preference. I'm right handed but I don't care that the arrow keys (which I use) are on the right side of the keyboard.

I usually let my GeForce Experience handle the settings and then turn off motion blur. I tend to play games on their default difficulty setting and with standard controls. So not much tweaking from me.

Set resolution to stun.... I mean 1080p (if possible).

Nowadays I play mostly from my livingroom on a 4k display but to keep fps high and temperatures and noiselevels in check I rather play at a sensible 1080p with v-sync enabled. And if I'm completely honest from 5 feet away I don't see the difference between 4k and 1080p (probably depreciating eyesight).

Other options are mostly setting anisotropy to 16x (insert 16x the detail meme) In my experience this hardly impacts performance and makes things look so much better as well as turning on/off other details like post effects (mostly off), anti aliasing (4 or 8x) and motion blur (mostly off).

After some playing I often change soundlevels and turn the volume of the music to a lower setting and if I don't like the music or it repeats too often I completely turn it off.

Anything like motion blur or bloom effects...those go away immediately.

I do this for sure when I first boot up a game!

Besides that, I often set the graphics presets on 'Medium' and play the game that way for my first session. Then, if the game performed well enough for my tastes, I bump it up to High on my second play session and further from there on subsequent plays if the performance continues to be stable.

However high this takes me, I almost always end up turning off most post-processing effects since I either don't notice them or find them annoying (especially motion blur), so I end up with the annoying 'Custom' preset...

The thing is, if I start tinkering too much, I notice how little I care for most graphical enhancements. I barely notice any changes as I switch between presets nowadays, and even obvious things such as shadows are lost on me since I tend to focus on the gameplay so much.

I find that newer (3D) games look a lot better on non-native resolution than the really old ones. My native res is 1440P but Control looked pretty good at 1080P. (just testing, I'm waiting for a new card before I really start playing it)
Neverwinter Nights on 1080P looked like it was covered with a layer of blur. I tried this before the EE was released, because the UI was too small for 1440P (on 27").