BEST UPGRADE regardless of cost?

Spectral Pre and amp with MIT cabling. Spectacular improvement over the other “so called” top level equipment I had. I’m forever greatful to the well known,well respected Michael Percy (Audio) for his knowledgeable guidance. (PS for those unaware; both Spectral and MIT have extraordinary engineering talent whose expertise is respected by those in other fields :). 

Acoustic treatment

I agree, treat your room!
The best upgrade I have done here.

Playing with speaker placement absolutely free, if you don't find improvement you can always replace to original location.

The speaker is the most inaccurate piece of gear in the system not to mention each one interacts with rooms differently 

the speaker is easily, hands down, the most variable product sound wise and thus has the most influence on how your overall system will sound. 

Fixing room acoustics is great, but a speaker that has muffled mids, or a recessed sound will always generally sound that way. 

It it makes me laugh when people say the front end is more important. It’s important no doubt, but unless your using the crappiest gear it’s not as important as the speakers.  This assumes there is no piece of gear in the system wildly out of synergy with the rest of the system. 

The the thing is I can put you in $100000 system with a $20000 amp $30000 set of speakers and change out the amp with a $1000 amp with the same power ratings, set it to the same dbl’s and you might notice some nuanced differences. But Change those speakers out to a different design type and there would be no doubt there are differences. 

The speakers make the biggest change in any given system assuming room acoustics are equal between systems.