Static site-wide configuration settings are probably best stored in configuration files (INI or XML). User specific configuration settings (ie. user specified theme, language selection) are probably better stored in a database (though you could just as well store these in uniquely named config files).
As for how hard it is to update the ini file : that will depend on the number of settings you store in it. To make this a bit easier on yourself you could create sections per module, so you can jump to the relevant section and quickly change the config vars.
ie.
[module1]
var1=value1
var2=value2
...
[module2]
varX=valueX
varY=valueY
...