Start by considering the worst case scenario and make sure that if that happens then maybe some of your gear will get wet, but the core stuff you will need to deal with this catastrophe will remain dry. For some people and/or trips this will only be that it rains for a long time. For other this will be your pack fall off, sinks to the bottom of a stream, and get stuck under a rock for half an hour.
For example I always have my bag and primary insulation layer, usually a down jacket, in a separately sealed dry bag. That way if I fall in a river (and presumably I would also need to roll down the river a mile or two) and my outer waterproof layer, whatever that is, is infiltrated, I can still set up my shelter and get into my dry jacket and bag while drying things out. With a totally reliable, immersion-proof inner protection for the bare minimum you can be as loosey-goosey with everything else as you like, and under most condition it will not matter. Throw away those ziplocks and unnecessary stuff sacks and so on, knowing that it will suck if the worst happen, but it will not be life threatening.
For a classic analysis of the paranoid extreme everyone should read this article by Jim Wood:
http://jwbasecamp.com/Articles/DryGear/index.html
Some of the actual technology analyzed is a bit out of date, but the basic principles are not. This is particularly useful in the way it systematically analyzes the risks and what to do about them – I think he is an engineer. I read his blog when I was just starting UL, even before there was a BPL, but sadly it seem to be inactive now. From this you can decide which level of paranoia to forego.