I would like to change almost ALL the default paths to custom ones, eg
Website path from: /var/www/clients/client[client_id]/web[website_id] to /home/client[client_id]/web[website_id]
If you do this, suexec will stop working so none of the cms systems installed in your sites will be able to write data or images to disk. The suexec path is compiled into apache, so if you would like to chnage the path in that way, you would have to compile your own apache server instead of using the one provided by the Linux distribution. Customs ettings that you do in ispconfig under system > server config will not be overwitten on updates, but you should really consider to not change the path in the way you described above as you will have many drawbacks then.