I think that your sentence I would like to add a bigskip before the content defined by the parameter #1
is not what you want. Parameter #1
is the optional parameter (initially empty) and will serve to add new options or change the already defined options for cvbox
. It's not related with box contents.
In case you wanted a \bigskip
between cvbox and previous paragraph, you should use before=\bigskip
option (which can be introduced as optional parameter when you need it)
\documentclass{article}
\usepackage[T1]{fontenc}
\usepackage[utf8]{inputenc}
\usepackage{lmodern}
\usepackage[most]{tcolorbox}
\usepackage{blindtext}
\newtcolorbox{cvbox}[2][]{%
blanker,
leftupper=4cm,
rightupper=2cm,
after skip=1cm,
title=\textcolor{blue}{\textbf{\uppercase{#2}}},
breakable,
#1
}
\begin{document}
\blindtext
\begin{cvbox}[before=\bigskip]{Example with bigskip}
\blindtext
\end{cvbox}
\newpage
\blindtext
\begin{cvbox}{Example without bigskip}
\blindtext
\end{cvbox}
\end{document}

But if you want the bigskip
between cvbox title and cvboxcontents, you should use before upper=\bigskip
option:
\documentclass{article}
\usepackage[T1]{fontenc}
\usepackage[utf8]{inputenc}
\usepackage{lmodern}
\usepackage[most]{tcolorbox}
\usepackage{blindtext}
\newtcolorbox{cvbox}[2][]{%
blanker,
leftupper=4cm,
rightupper=2cm,
after skip=1cm,
title=\textcolor{blue}{\textbf{\uppercase{#2}}},
breakable,
#1
}
\begin{document}
\blindtext
\begin{cvbox}[before upper=\bigskip]{Example with bigskip}
\blindtext
\end{cvbox}
\newpage
\blindtext
\begin{cvbox}{Example without bigskip}
\blindtext
\end{cvbox}
\end{document}

#1
is supposed to be a valid key-value list. What do you mean by prepending\bigskip
to a list of key-value settings?