Here's one for the academic geeks... After many years of using Endnote, I've finally switched to using BibDesk to organise my references. This will probably make me sound prehistoric, but when I did my PhD I used 3 x 5 index cards in a box to file my references. This had certain advantages — you could pop down to the library with a stack of blank cards and fill the details in as you did your reading — but they were hell to search. Things were fine if you could remember the first author, but if you only knew one of the authors, or part of the title, you were sunk. And then there was the whole dropping the entire box on the floor and having to resort the references thing — not a good use of time.
So, when I switched to Endnote, it felt like a huge step up. There has always been a bit of a reference manager divide between the Physical Sciences and the Biosciences. Physicists, mathematicians and engineers tend to use LaTeX to write their papers (because of the all the equations, for one thing), so naturally use BibTeX to organise their references. Biologists tend to use Word (ack), and so use Endnote. I wish that this wasn't the case, because BibTeX has a lot to recommend it. The files are just structured plain text, so there's no fear that years of research will be locked into a corrupted, proprietary format. For the same reason, it's easy to send colleagues snippets of text that can just be pasted into their *.bib files, already in the right format.
I'm writing in LaTeX much more now, so I felt that the time was right to switch. Endnote has felt more and more elderly, bloated and unloved over the years, and I'm happy to see the back of it. BibDesk is Open Source, and has great Applescript support, so even if you're not using LaTeX, you can fairly easily knock up a script to print out your reference list nicely.
While I'm on the subject of references, I've also really got in to using CiteULike. It's similar to del.icio.us, but geared towards academic references. It has tags, and the social nature of the system means that you often pick up interesting references by surfing other people's tags. We have a reading group at work, and it's really handy to list and tag the papers we're going to read on CiteULike, so that everyone has the full information. As a bonus, it's really easy to import or export references as BibTeX (or Endnote, but I haven't tested that).