We went to Apache 2.x/Php 5.x + suPHP from Apache 1.x/PHP 4.x on all our shared boxes and had very minor issues.
The biggest issues for us were:
Files owned by "nobody".
*Check Gallery and Soholaunch installations
Fixed with this simple script from another thread (sorry, don't remember the persons name that posted it):
Users with php configuration values in their .htaccess files.
for user in *
chown -R $user.$user /home/$user/public_html/*
Some configuration lines won't work with suPHP - at least, not within the .htaccess file. In particular, "php_value" and "php_flag" values.
You must move all lines beginning with "php_value" and "php_flag" from the .htaccess file into a file called php.ini (in the public_html directory). Then you must add a line to the .htaccess file like the one below (of course "username" being your actual username).
You will need to remove php_value and php_flag from ALL .htaccess files you may have. However, you only need to add the suPHP_ConfigPath line in the .htaccess file in the public_html directory.
Hope this helps!