Hi lychina,
You would indeed be making a “best guess” unless you have tested the specific combination you end up buying. Every variable or combination that you haven’t tested introduces some level of uncertainty. Every layer of a mattress will affect every other layer and the same topper on two different mattresses can feel very different depending on the design of the mattress underneath it. In addition to that … different people would feel any differences differently depending on what they tend to feel the most (see post #15 here about “species” of softness). Of course the more testing you have done on many specific combinations the more educated your “guesses” will be. For example if you have tested a 3" 24 ILD latex topper with wool on three different 6" latex base layers (say 28 ILD, 32 ILD, and 36 ILD) that only differ in ILD not type of latex and then tested a 3" 24 ILD topper without wool on the same base layers and spent about 15 minutes on each mattress (6 different mattresses) you would probably have a fairly educated intuition about how that particular 3" layer in 24 ILD as a topper would affect mattresses where you hadn’t tried the specific combination. you would be much better prepared to guess at combination you hadn’t personally tried. This type of testing would take a lot of time and would require the individual materials and components to even be available so for most people this type of testing to this degree of detail may not be practical in terms of either time or availability and quite frankly many people may not even be sensitive enough to notice much difference in some of the combinations anyway.
Yes … as you are mentioning the two sided version would feel different to some people (and perhaps not to others). This is all part of the “art and science” of mattress design and one of the reasons it helps to be working with knowledgeable people although no matter how much knowledge and experience they have, nobody can predict with absolute certainty how any changes will affect specific people.
Some people are somehow able to sleep on anything and practically every mattress seems to feel the same or similar to them. Other people will notice what they call major differences between seemingly very small variations.
Phoenix