I used to have about 700 PDFs scattered over my hard drive. Then I got Papers. It is made for the sciences particularly, but I still get full-functionality from it as a user in the Humanities. I also set it to rename and move the files to one main folder upon import. It basically looks like iTunes for PDFs and performs full-text searches of my now-over 1000 PDFs (mostly journal articles, Google Books, and my own book scans, as I like to scan the introduction and, sometimes, the bibliography of books).
However, Papers doesn't do citations so I also use EndNote (X3) and it's easy to import/export between the two. I have Sente, as well, but have never really warmed to it. On the other hand, I am also testing out another Mac citation manager, Bookends, which I could see myself using rather than EndNote at some point. Of course, if you're using Windows this information is less-than-valuable. Before I switched from Windows to OSX, I used Mendeley for PDFs and EndNote X2.
Like collegekidsmom said, spend some time developing a workflow. I have spent a lot of time in the last year trying to figure out the most productive workflow for myself. This included managing my PDFs, citation libraries, note-taking software, etc.... It takes a while to experiment with trial versions of different programs, but, five years down the road, it will be worth it.