Alignment of multiple figures in rows and columns

The [t] option uses the baseline of the first line (same as minipage). You can see the baseline using \leavevmode\rlap{\rule{\textwidth}{1pt}}. So subfigures using [t] are actually aligned by the bottoms of the images, not the tops. To align the tops you would need \raisebox{-\height}{...} on every image.

\documentclass[12pt,a4paper,twoside, draft]{article}
\usepackage{graphicx}
\usepackage{subcaption} %to have subfigures available

\begin{document} 
\begin{figure}
     \centering
    \begin{subfigure}[t]{0.49\textwidth}
        \raisebox{-\height}{\includegraphics[width=\textwidth]{img1.png}}
        \caption{caption of first image}
    \end{subfigure}
    \hfill
    \begin{subfigure}[t]{0.49\textwidth}
        \raisebox{-\height}{\includegraphics[width=\textwidth]{img2.png}}
        \caption{caption of second image\\second line}
    \end{subfigure}
    %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%second row
    \begin{subfigure}[t]{0.49\textwidth}
        \raisebox{-\height}{\includegraphics[width=0.49\textwidth]{img3.png}}
        \raisebox{-\height}{\includegraphics[width=0.49\textwidth]{img4.png}}%
        \vspace{.6ex}
        \raisebox{-\height}{\includegraphics[width=0.49\textwidth]{img5.png}}
        \raisebox{-\height}{\includegraphics[width=0.49\textwidth]{img6.png}}
        \caption{caption of the four small images\\second line\\third line}
    \end{subfigure}
    \hfill
    \begin{subfigure}[t]{0.49\textwidth}
        \raisebox{-\height}{\includegraphics[width=\textwidth]{img7.png}}
    \caption{caption of last image\\second line} 
    \end{subfigure}
    \caption{caption of main figure}
\end{figure}
\end{document}