The best person to answer this is Audioconnection- Johnny R.
1. Distance from listener to plane of speakers, or
2. Distance from listener to each speaker.
Better yet, Mr. V.
For me, I think #1 is the correct way.
Tilt is truly critical for the Vandersteens, for imaging and tonality, so spend the time to get it right.
I owned Quatro's for a happy while, and I found that the foolproof way to get this done in my room was to use a level with a laser pointer. I would set this level on top of the wooden cap and project the beam to where my listening position was. There I had paper on a stand that the beam illuminated, and I would mark the location of Ear Height + Offset (from Tweeter to Laser position on the Cap). When I got the beam to hit that point, everything snapped into focus amazingly well, with proper tonality, importantly. Get this right on one side and then tilt the other to match the same spot.
Do the measurements as per the manual but also allow for some "wiggle room" based on your listening preferences. In my personal listening experiences and those of others with whom I've corresponded, the consensus is that tilting back just a slight bit more than measurements would indicate can yield a very satisfying sound...a bit less treble emphasis. Doing the opposite can accentuate the treble to a slight degree. It's all a matter of taste. Some like it hot, some not!
My understanding of the procedure was the measurements are from the "acoustic center" of the speaker. I've had 2Ci, 3A Signature and now 5's, as I recall for the 2 & 3 series the "acoustic center" is in the middle of the top plate. For the 5's the "acoustic center" is in the middle, front edge of the fabric hood that covers the woofer, midrange and tweeter.