For me, it would have to be rsync. I’ve yet to find anything that comes close in terms of keeping me backed-up and in sync across different machines.
Add the grsync frontend and it’s just a magical piece of software, fast too. I still wince when I have to copy and sync within windows. 
I started thinking about this and found myself thinking: What if there was no Firefox (I could use Opera, Seamonkey, Konqueror) But actually I already use all those, I just prefer FF.
The app I use quite a bit ATM and really has no alternative: get_iplayer
Next would be the much criticised recently: k3b
A web browser. After that, a mail program.
@ken_yap
+1, and after that a financial data application e.g. Quicken (using wine).
A web browser (FF)… after that OpenOffice writer and Kate.
Laugh if you will. An old text-based database language called Sculptor running in the MESS 6809 emulator, running under Suse. Faster that greased lightning!
a CAD program… using autocad 2008 with wine now… wating for bricscad 9 for linux to release!
A web browser, a shell, mplayer/mencoder and a music program (doesn’t matter which one as long as it doesn’t suck that much) 
I do not need local mail programs since I use gmail for that. Oh yeah and a text editor, preferably kwrite and nano for CLI
I would go crazy without SSH!>:)
An operating system 
Can you run ACAD2008 with wine stably? I think that’s not possible. Even ACAD2000 won’t.
Bricscad may be the answer, sort of, without all the cool 3D stuff. Last time I tried it (version 6 or 7), it wouldn’t run in opensuse, only Mandriva IINM.
XEmacs. I’ve burned far too many of the the commands and way of working into my brain.
I use vi too BTW, this isn’t an excuse for a holy war.