Consider the Hamiltonian for a single particle in some potential
$$H(p,q) = \frac{p^2}{2m} + V(q)$$
where the first term is the kinetic energy and the second term is the potential energy. In this case, we have
$$\frac{\partial H}{\partial q} = \frac{\partial V}{\partial q}$$
On the other hand, the momentum is
$$p = mv$$
where $m$ is the mass and $v$ is the velocity, so
$$\dot{p} = \frac{d}{dt}{m v} = m\dot{v} = m a$$
where $a$ is the acceleration. In this case, the Hamilton equation
$$-\dot{p} = \frac{\partial H}{\partial q}$$
becomes
$$-m a = \frac{\partial V}{\partial q}$$
If we now use Newton's second law
$$F = ma,$$
we get $$F = - \frac{\partial V}{\partial q}$$
If we didn't have the minus sign in the Hamilton equation, we wouldn't have the minus sign here. It tells you that the Force associated with a potential always acts in the direction which makes it smaller. (If $\partial V/\partial q$ is positive, that means $V$ gets larger when $q$ becomes larger, so $F$ acts in the opposite direction.)
This is why things fall down. Because the gravitational potential gets lower in that direction. If the minus sign wasn't there, everything would fall up instead of down. So it's pretty important in keeping the universe together.