I have a tough time with this every year. My portfolio is not nearly as large as that of some companies, but paying registration fees on over 1000 domains every year takes a toll, especially with parking income falling. I've had to make some tough decisions lately and I've let some of my weaker domains drop. Here's how I made those decisions.
1. Keep two word dotcoms that make sense. Most of my domains are two word health-related .coms that I picked up during the .com crash. These have retained value and I believe that they will continue to be valuable. I sell enough every year to stay afloat.
2. Dump the .net and .org versions when you own all three extensions. For a while I owned a number of domains in the .com, .net, and .org version, thinking that a buyer might want to corner the market on that domain. Rarely does that happen. As the new tlds have emerged these .net and .org domains can be let go. There is just no demand.
3. Dump new tlds unless they are really spectacular one-word domains. It's going to take a while for a real secondary market to develop with most of these tlds. I've recently seen a huge uptick of spam that uses .xyz as the originating domain. I guess .xyz is the new .info.
4. Dump most typos and domains that "seemed like a good idea at the time." I bought a bunch of domains that ended with "superstore" back when SmartName Shops were doing well. Nothing much happened with them. I recently decided to let these go, even though someone made an offer (with a bad email address) on BidetSuperStores.com. I was the Mental Health Resources on About.com for several years and afterward I bought a bunch of names that began with the word about. Nobody was interested. I allowed these to expire.