The answer to this question rests in linear algebra. If $f$ is twice continuously differentiable (just to avoid pathological things) then we have that partial derivatives of $f$ commute. I'll skip the proof, but, the same goes for the directional derivatives of $f$. We have $D_u(D_v f) = D_v(D_u(f))$. Furthermore, if $u,v$ are linearly independent then they form a basis for $\mathbb{R}^2$ and we can study the behavior of the quadratic term in the multivariate Taylor expansion in terms of the theory of quadratic forms. In particular,
$$ Q(h,k) = [h,k]\left[ \begin{array}{cc} D_uD_uf & D_uD_v f \\
D_uD_v f & D_vD_v f \end{array} \right]\left[ \begin{array}{c}h \\ k \end{array} \right] = \lambda_1\bar{x}^2+\lambda_2\bar{y}^2$$
where $\bar{x}, \bar{y}$ are eigencoordinates and $\lambda_1, \lambda_2$ are the eigenvalues of $A = \left[ \begin{array}{cc} D_uD_uf & D_uD_v f \\
D_uD_v f & D_vD_v f \end{array} \right]$. Using linear algebra and the specific form of $A$,
$$ \text{trace}(A) = \lambda_1+\lambda_2 = D_uD_uf+D_vD_vf $$
and
$$ \text{det}(A) = \lambda_1\lambda_2 = (D_uD_uf)(D_uD_uf)-(D_uD_vf)^2$$
If $\nabla f =0$ at a point then $f(p+(h,k)) = f(p) + Q(h,k)+ \cdots $ which means that the nature of $z = f(x,y)$ near $p$ is totally governed by $Q$. It's easy to see
- If $\lambda_1\lambda_2 <0$ then $f$ is both increasing and decreasing near $p$ hence we face a saddle point. Specifically, in terms of directional derivatives, $(D_uD_uf)(D_uD_uf)-(D_uD_vf)^2 < 0$ provides $\text{det}(A)<0$ and hence the eigenvalues differ in sign.
- If $\lambda_1, \lambda_2>0$ then $f$ increases as we travel away from $p$ this is manifest from the formula $\lambda_1\bar{x}^2+\lambda_2\bar{y}^2$ for $Q$. This requires $(D_uD_uf)(D_uD_uf)-(D_uD_vf)^2 > 0$ and $\text{trace}(A) >0$, but, if you think about it, given $\text{det}(A)>0$ we have $D_uD_u f>0$ implies $D_vD_v f>0$. In short, if $(D_uD_uf)(D_uD_uf)-(D_uD_vf)^2 > 0$ and $D_uD_u f>0$ then $f$ has a local minimum at $p$.
- If $\lambda_1, \lambda_2<0$ then $f$ decreases as we travel away from $p$ this is manifest from the formula $\lambda_1\bar{x}^2+\lambda_2\bar{y}^2$ for $Q$. This requires $(D_uD_uf)(D_uD_uf)-(D_uD_vf)^2 > 0$ and $\text{trace}(A) < 0$, but, if you think about it, given $\text{det}(A)>0$ we have $D_uD_u f<0$ implies $D_vD_v f<0$. In short, if $(D_uD_uf)(D_uD_uf)-(D_uD_vf)^2 > 0$ and $D_uD_u f<0$ then $f$ has a local maximum at $p$.
At this point, you may complain, I meant to study $f: \mathbb{R}^n \rightarrow \mathbb{R}$. What is the significance of mixed directional derivatives in that context for $n>3$. It's more complicated, to give the complete picture, I need $n$-LI directions and all $n(n+1)/2$-independent mixed directional derivatives. If I have all that data then I can construct the $n \times n$ analog of $A$ and again characterize the nature of the graph $x_{n+1} = f(x_1, \dots , x_n)$ at a critical point in terms of the eigenvalues of $A$ (assuming $A \neq 0$, in the case $A=0$, we'd need higher derivative data...)
Another way to look at my answer is this: the mixed directional derivatives also have to do with concavity. The eigenvalues tell us the concavity of the sections of the graph in the direction of eigenvectors. If the point is critical, then that concavity reveals the extremal nature of the point.