I've culled the collection twice. The first time was to get rid of a whole lot of stuff that I was sure I would never use again - games I'd never played or just didn't like, orphaned supplements, loads of d20 dross, and so on. That got rid of about two shelves of stuff, and left me with a smaller, but higher quality, collection.
The second time was to get rid of all of my hardcopy Pathfinder material (except adventures) - I'd tried it in the interim and decided that is just wasn't for me.
In both cases, I gave my extended RPG group first refusal, and gave what was left to a charity store.
The third cull, if it comes, will almost certainly be to get rid of a lot of old magazines. I'll probably keep Dragon and Dungeon for nostalgia's sake, but the same can't be said for White Dwarf, Arcane, Backstab, and the like.