Just thinking out loud…
“Difference” implies “different-from.” Something that is is different from what it is not. Doesn’t it follow that the discrete uniqueness of an object, its essence as “different,” is defined in relation to everything else from which it differs? This isn’t just a language game, where the word for an object is defined as its difference from all other words. Nor is it just an epistemological matter, whereby an observer recognizes a discrete object relative to its surroundings. If something isn’t different from other stuff, then it’s the same as the other stuff, no?
If a reality is entirely uniform and stable, then any sort of change that emerges in this reality is differentiating. If a reality is entirely chaotic, random, noisy, unstable, then any sort of stability that emerges in this reality is differentiating. If a reality is comprised entirely of discrete things, stable yet distinct from one another, then any sort of unique pattern is differentiating. In any case, difference is different-from.
If difference is that which distinguishes a thing from the rest of the reality it occupies, then the uniqueness of a discrete thing is the combination of differences it contains. This n-dimensional differential vector might manifest itself in a variety of ways relative to other things in its larger reality. So, for example, a distinct genetic pattern will generate an organism that exhibits various kinds of distinct phenotypic differences in the ways it interacts with its environment. Whether one regards genotype or phenotype or both as the definitive “difference that makes a difference,” in any case the essence of the discrete organism is still embedded in the vector of differences-from, which are intrinsically relational.
Suppose the essence of some discrete thing withdraws from all relations. If difference is always relational, then difference makes no difference to this discrete thing: it could hypothetically be identical to anything or everything else in its reality and still be a discrete thing in its withdrawn essence. Conversely, a thing’s difference-from other things can be multiple and extreme yet still not make any real difference for establishing its distinct reality. The only alternative I can think of is to propose a kind of difference that isn’t difference-from. The interior of a discrete thing into which its non-relational essence retreats: it would have to be a place outside of the reality in which relations occur, wouldn’t it?