For the nodes to have the same width, you need to set a common text width or a common minimum width for all.
If text width is set too small, text will protrude outside the node. If the chosen minimum width is too small, it will simply get ignored.
You can also use the PGFmath function width, e.g.
text width={width("$\mathsf{sk}_{f, t}
= iO(\text{PKey}[\mathsf{sk}_0^{\mathsf{PKE}}, t])$")}
but that can get annoying if you might change your formulas later.
On the second frame, I'm using my ext.node-families library which does the measuring for you but it will need two compilation runs. Here I'm using the same family name for all nodes which means that even the left nodes are the same width as the right nodes (and not only those in the same column).
I think the best approach for this is the aligned environment which is basically the inline version of the align environment. (This means the left side is not aligned left but I don't think this is desirable. Though you can also use alignat's little brother alignedat.)
You can use the normal font-switching commands \small, \footnotesize, \scriptsize and \tiny to get smaller text (and in turn a smaller diagram). Though I don't think this is a good idea since you need a really small size to get four of those on one page.
You can also use the scale transformation of TikZ but that doesn't really make it better.
The hf-tikz package defines \bcol and \fcol when its options are used so we can use this for our real nodes, too, to simulate its effect. Unfortunately, there's no nice style that can be used to apply all settings the hf-tikz package provides.
I'm using a \matrix (of math nodes) on the second frame which to me makes it a bit cleaner to write down and display those formulas.
Code
\documentclass[xcolor=table,10pt,aspectratio=169]{beamer}
\usetheme{metropolis}
\usepackage[T1]{fontenc}
\usepackage[american]{babel}
\usepackage{amsmath,amssymb,amsthm}
\usepackage[beamer]{hf-tikz}
\usetikzlibrary{
matrix,
positioning,
ext.node-families,
}
\DeclareMathOperator{\Enc} {Enc} % instead of \mathsf{Enc}
\DeclareMathOperator{\PKey} {PKey}
\DeclareMathOperator{\Sim} {Sim}
\DeclareMathOperator{\Prover}{Prover}
\begin{document}
\begin{frame}{Intuition}
Guessed \texttt{minimum width}
\begin{center}
\begin{tikzpicture}[nodes={draw=\bcol, fill=\fcol, rounded corners, minimum width=4.5cm}]
\node[] (A) {$\begin{aligned} c_0 & \gets \Enc(\PKey_0^{\mathsf{PKE}}, m_0) \\
c_1 & \gets \Enc(\PKey_1^{\mathsf{PKE}}, m_0) \\
\pi_{t^*} & \gets \Prover(t^*, x, w) \end{aligned}$};
\node[below=0.1cm of A] (C) {$\mathsf{sk}_{f, t} = iO(\text{PKey}[\mathsf{sk}_0^{\mathsf{PKE}}, t])$};
\node[right=1cm of A] (B) {$\begin{aligned} c_0 & \gets \Enc(\PKey_0^{\mathsf{PKE}}, m_0) \\
c_1 & \gets \Enc(\PKey_1^{\mathsf{PKE}}, m_0) \\
\pi_{t^*} & \gets \Sim(t^*, x) \end{aligned}$};
\node[below=0.1cm of B] (D) {$\mathsf{sk}_{f, t} = iO(\text{PKey}[\mathsf{sk}_0^{\mathsf{PKE}}, t])$};
\end{tikzpicture}
\end{center}
\end{frame}
\begin{frame}{Intuition}
\texttt{\string\matrix} and \texttt{ext.node-families} (needs two compilations)
\begin{center}
\scriptsize
\begin{tikzpicture}
\matrix[
nodes={draw=\bcol, fill=\fcol, rounded corners, node family/width=samewidth},
matrix of math nodes,
ampersand replacement = &,
row sep=.1cm,
column sep=.2cm] {
\begin{aligned} c_0 & \gets \Enc(\PKey_0^{\mathsf{PKE}}, m_0) \
c_1 & \gets \Enc(\PKey_1^{\mathsf{PKE}}, m_0) \
\pi_{t^} & \gets \Prover(t^, x, w) \end{aligned}
&
\begin{aligned} c_0 & \gets \Enc(\PKey_0^{\mathsf{PKE}}, m_0) \
c_1 & \gets \Enc(\PKey_1^{\mathsf{PKE}}, m_0) \
\pi_{t^} & \gets \Sim(t^, x) \end{aligned}
&
\begin{alignedat}{3} & c_0 && \gets \Enc(\PKey_0^{\mathsf{PKE}}, m_0) \
& c_1 && \gets \Enc(\PKey_1^{\mathsf{PKE}}, m_0) \
& \pi_{t^} && \gets \Prover(t^, x, w) \end{alignedat}
&
\begin{alignedat}{3} & c_0 && \gets \Enc(\PKey_0^{\mathsf{PKE}}, m_0) \
& c_1 && \gets \Enc(\PKey_1^{\mathsf{PKE}}, m_0) \
& \pi_{t^} && \gets \Sim(t^, x) \end{alignedat}
\
\mathsf{sk}{f, t} = iO(\text{PKey}[\mathsf{sk}_0^{\mathsf{PKE}}, t])
&
\mathsf{sk}{f, t} = iO(\text{PKey}[\mathsf{sk}_0^{\mathsf{PKE}}, t])
& \text{too small} & \text{to read}
\};
\end{tikzpicture}
\end{center}
\end{frame}
\end{document}
Output

text widthorminimum widthfor both nodes. Or Q107277. 2.align=left. For more control, useamsmath'salignedator anarray. 3. Simply use\smallor any other size command. Either at the start of the tikzpicture, at the start of the text of the node orfont=\small. 4.draw=green, fill=green!50, rounded corners.