Basically I have 4GB of RAM (on the latest MBP) and regularly run: Netbeans IDE, Safari (and a bunch of tabs), Firefox (ditto on the tabs), an FTP client, a Subversion client, iChat, Mail, a notes app, alarm clock, Dropbox, Evernote, terminal, one other text editor (MacVim or Textwrangler), Photoshop, MS Word, a clipboard app and sometimes VirtualBox running Windows XP (with 1GB of RAM assigned).
The killers seem to be Netbeans and VirtualBox. Once I have those both going I know I'm in for a reboot before too long.
I assume it's just a RAM issue but it is annoying that 4GB isn't "enough" (assuming I'm correct about why I have to reboot).