I really think the following one is just intuitive. However, not only is it consistent to be false in ZFC, it is actually not known to be consistent in ZFC (its consistency follows from the existence of a weakly compact cardinal).
The conjecture is second-order, and thus must be regarded in NBG rather than ZFC, though I think this isn't too much of a cheat for the question. Furthermore, the negation of this conjecture is only known to be consistent as long as there is a worldly cardinal. A meager assumption nonetheless, but still quite a jump from ZFC in consistency strength.
Let $D$ be the class of all doubletons of ordinals (i.e. $\{\alpha,\beta\}$ such that $\alpha<\beta$). Let a class $H\subseteq D$ be containable iff there is some class $h$ such that every element of $H$ is a subclass of $h$ and every doubleton of $h$ is an element of $H$. The Doubleton Ordinal conjecture is as follows:
For any proper class $X\subseteq D$, there is a containable proper class $H\subseteq D$ such that either $H\subseteq X$ or $H$ is disjoint from $X$.
Although this seems quite reasonable, it does not hold in $V_{\kappa+1}$ (the successor of $\kappa$ is used for second-order logic) for the least worldly cardinal $\kappa$. This is quite a strange result indeed.
In fact, $V_{\kappa+1}$ satisfies the Doubleton Ordinal conjecture iff $\kappa$ is $0$, $\omega$, or weakly compact.