There are ways to study the relation between self-adjoint Hamiltonian operators and unitary evolutions. Mathematically, there is a one-to-one correspondence between strongly continuous unitary representations of the reals (seen as an abelian group) $(U(t))_{t\in\mathbb{R}}$ and self-adjoint operators on the Hilbert space $\mathscr{H}$ of the representation.
So given any self-adjoint operator of the form $H=-\Delta +V(x)$ with domain $D(H)$ on the Hilbert space $L^2(\Omega)$, $\Omega\subseteq \mathbb{R}^d$, there is one strongly continuous representation of the reals generated by it, and often denoted by $(e^{-i\frac{t}{\hslash}H})_{t\in\mathbb{R}}$. So considering the dynamical quantum system $\Bigl[\mathscr{B}\bigl(L^2(\Omega)\bigr),(e^{-i\frac{t}{\hslash}H}\,\cdot\, e^{i\frac{t}{\hslash}H})_{t\in\mathbb{R}}\Bigr]$, composed of an algebra of observables (the continuous operators on the Hilbert space) and an automorphism of time evolution, the observable $H$ generates the dynamics and it is left invariant by it.
Conversely, given a dynamical system $[\mathcal{W}, (U(t)\,\cdot\,U^*(t))_{t\in\mathbb{R}}]$ where $\mathcal{W}\subseteq \mathscr{B}(\mathscr{H})$ is a W*-algebra and $(U(t))_{t\in\mathbb{R}}$ is a strongly continuous group of unitary operators on $\mathscr{H}$, then the generator of time evolution, left invariant by it, is given by $H=\frac{d}{dt} U(t)\Bigr\rvert_{t=0}$ (where the derivative is taken in the strong operator sense in a suitable dense domain). $H$ is a self-adjoint operator on $\mathscr{H}$.