The g
(global) ex command does what you want:
:g!/^#/s/^I/+/g
The general format is g [!] /RE/ CMD, where RE is a pattern describing all the lines to apply the command to and CMD is any ex command. The optional ! reverses the sense of the RE, applying the command to all lines that DON'T match.
To get a TAB character on the line (the ^I
above), you need to hit ctrl+V followed by TAB