I am looking for a good solution to override the Magento config without changing the default values.
For example, I want to override the \"web/unsecure/base_skin_url
Alan's answer is correct, but it doesn't care about the config cache. For example, if you call Mage::getStoreConfig('web/unsecure/base_skin_url') twice and change the value in between, the change has no effect.
To get around this issue, you should use $store->setConfig('web/unsecure/base_skin_url', 'value_to_set'). It does both: update the config cache and set the config node with Alan's method.