The code adds some completely useless invisible (or rather white) stuff. The lines
\clip(0pt,403pt) -- (389.957pt,403pt) -- (389.957pt,99.6166pt) -- (0pt,99.6166pt) -- (0pt,403pt);
\color[rgb]{1,1,1}
\fill(3.76406pt,399.236pt) -- (380.923pt,399.236pt) -- (380.923pt,253.19pt) -- (3.76406pt,253.19pt) -- (3.76406pt,399.236pt);
\fill(53.4497pt,394.719pt) -- (374.901pt,394.719pt) -- (374.901pt,289.325pt) -- (53.4497pt,289.325pt) -- (53.4497pt,394.719pt);
draw a white background that is larger than the actual picture. TikZ sees that and thinks it is part of the picture. Simply removing/uncommenting these lines removes most of the whitespace.
Near the end of the first scope,
\color[rgb]{1,1,1}
\fill(3.76406pt,249.426pt) -- (386.193pt,249.426pt) -- (386.193pt,103.381pt) -- (3.76406pt,103.381pt) -- (3.76406pt,249.426pt);
does the same.
Additionally (near the end of the second scope
),
\pgftext[center, base, at={\pgfpoint{220.95pt}{106.392pt}}]{\sffamily\fontsize{9}{0}\selectfont{\textbf{ }}}
adds a blank node below the picture, again enlarging the bounding box.
Removing all those lines gives a tight bounding box.
As far as I know, TikZ cannot do the cropping for you, as it can't know whether the white stuff is intentional or not (there might for example be a dark background behind the image so that white is visible).
I don't really get the question so I hope this is what you wanted. If you include a full document (such that we copy paste and see the problem on our systems) things are much more easier.
Here, you can change the default setting within a scope but your block
style had a node distance
which was resetting every time it is issued. I've made it 2mm such that we can see the difference easier.
\documentclass[tikz]{standalone}
\usetikzlibrary{arrows,shapes.geometric,positioning}
\begin{document}
\begin{tikzpicture}[decision/.style={diamond, draw, text width=4.5em, text badly centered, node distance=3.5cm, inner sep=0pt},
block/.style ={rectangle, draw, text width=6em, text centered, rounded corners, minimum height=4em, minimum height=2em},
cloud/.style ={draw, ellipse, minimum height=2em},
line/.style ={draw,-latex'},
node distance = 1cm,
auto]
\node [block] (1st) {1st};
\node [block, right= of 1st] (2nd1) {2nd1};
\begin{scope}[node distance=2mm and 10mm]%Here we change it for everything inside this scope
\node [block, above= of 2nd1] (2nd2) {2nd2};
\node [block, below= of 2nd1] (2nd3) {2nd3};
\node [block, right= of 2nd1] (3rd1) {3rd1};
\node [block, above= of 3rd1] (3rd2) {3rd2};
\node [block, above= of 3rd2] (3rd3) {3rd3};
\end{scope}
\node [block, below= of 3rd1] (3rd4) {3rd4};
\node [block, below= of 3rd4] (3rd5) {3rd5};
\path [line] (1st) -- (2nd1);
\path [line] (2nd1) -- (2nd2);
\path [line] (2nd1) -- (2nd3);
\path [line] (2nd2) -- (3rd3);
\path [line] (2nd1) -- (3rd1);
\path [line] (1st) -- (2nd1);
\end{tikzpicture}
\end{document}

Best Answer
As documented in the manual, the
rectangle split part align
key could help here. By default it is set tocenter
so all the boxes that contain the node part contents are aligned by their centers, but I expectbase
is what is required.However, what does seem to be a bug, is that the alignment doesn't affect the first part.