Right now (and this is a rather new way of doing things for me, so time will tell), I take notes on my index cards. If they are actionable, I copy the contents into my GTD system and discard the original. I store reference cards in a card box. Each card gets its own unique label, by date and time, and the cards are stored chronologically. I then use TiddlyWiki to index the cards by keywords. Hawk Sugano's reference system is entirely built with index cards, and he has some good ways to organize them.

Not to get off topic, but this sort of goes along with reference material and information retrieval.
I feel as though I'm really good with GTD. The majority of stress I feel from what I need to do comes not from what needs to be done, but from my reference system. I've tried moleskines, legal pads, manila folders, Evernote, and, most recently, TiddlyWiki. I just can't find a trusted, low-maintenance way to deal with random bits of information. I prefer to keep things lo-fi since technology is ever-changing and therefore unreliable for long-term storage. I worry that solutions like EverNote and TiddlyWiki will be obsolete in 5 years. Paper, on the other hand, is reliable, but difficult to index and retrieve information later. I love writing in moleskines, but the information is linear. Index cards are not as portable in bulk, but great for fleshing out relationships between bits of data. I have a selection of academic notes, meeting notes, and general reference. I would be interested to see how others have tackled this problem.

I feel as though I just need to stop worrying about this particular part of my system so much.