Natural candidate against the Isomorphism Conjecture? The famous Isomorphism Conjecture of Berman and Hartmanis says that all $NP$-complete languages are polynomial time isomorphic (p-isomorphic) to each other. The key significance of the conjecture is that it implies $P\neq NP$. It was published in 1977, and a piece of supporting evidence was that all $NP$-complete problems known at the time were indeed p-isomorphic. In fact, they were all paddable, which is a nice, natural property, and implies p-isomorphism in a nontrivial way.

Since then, the trust in the conjecture deteriorated, because candidate $NP$-complete languages have been discovered that are not likely to be p-isomorphic to $SAT$, although the problem is still open. As far as I know, however, none of these candidates represent  natural problems; they are constructed via diagonalization for the purpose of disproving the   Isomorphism Conjecture.

Is it still true, after nearly four decades,  that all known natural $NP$-complete problems are p-isomorphic to $SAT$? Or, is there any conjectured natural candidate to the contrary?
I think the answer is yes, even today there is no known natural problem that is a candidate for violating the Isomorphism Conjecture.

The primary reason is that typically natural NP-complete problems are very easily seen to be paddable, which Berman and Hartmanis showed suffices to be isomorphic to SAT. For natural graph-related problems this typically involves adding extra vertices that are, e.g., disconnected from the graph, or connected in a very particular (but usually obvious) way. For the decision version of optimization problems, it typically involves adding new dummy variables with no constraints on them. And so on.