I've tried a fair few tweaks, I include the free stuff like speaker positioning in there too and I'm also in the camp that everything matters to some degree. How much difference is going to be tweak and system dependant.
Some tweaks can deliver huge benefits for relatively low cost and some are punching about their weight, there are others which deliver much less bang for the buck.
The value proposition is always a personal one.
Equipment manufacturers always offer a range of gear , they manufacture to a price and they want to have a clearly audible difference between their entry level, thier 2nd tier and subsequent tiers (if they go that far).
In my opinion some tweaks can close the gap in equipment tiers and in some cases eliminate that gap totally.
If your total system budget is tight there are still loads of low cost/free tweaks you can do that will deliver bang for your buck. See Mahgister's system.
If your happy spending many 10s of thousands of dollars for you system then many more of those tweaks become cost effective, but for some folks they will never be happy until have the top tier equipment in their system (and in many cases that means they are paying a premium in my opinion).
Personally I really enjoyed fine tuning my system with tweaks. My system is low resolution source material but it sounds incredible (3D soundstage, PRaT, microdynamics, accurate tonality)
For reference my total system cost is about £10500 ($13000).
Cabling, fuses, clean power, and resonance control £3500.
Speakers £2000.
Amplifier and source (mine is 1 box streaming amp and it takes care of my room to boot with dsp) £4250
Source Apple TV 4th gen £160
Etherregen (audiophile network switch) £660
Enjoy the music everyone.