EGN  Have tried others but for me this is the best one. Not because it's free, but because the ease of use and options make it the best one. Excellent time saver.  
(Version 3.0b9)

THECAUSE  Excellent software. Easy to use. Hides so you set it, forget about it, and can still use it. Ideal for the older Bondi Blue macintosh keyboards which don't have volume controls.  
(Version 3.0b9)

POIKKEUS  You can pay for HotApp, or use Butler for free, but hot-keys are a useful time-saver to make it easier to get your work done more quickly. For me, Spork has several advantages:

1. It's free

2. It's intuitive, and can be used almost instantly

It takes about five minutes to configure. Instead of using the dock, a single keystroke will bring you Mail, Safari, or whatever application or action you have in mind. I've found it very stable for OS 10.5.  
(Version 3.0b9)

XENOS  no idea what i'm doing wrong with all versions lately issued: the app always would quit right after launching - as much as i would like to try it out:

PPC G4 Quicksilver 2001, 733 Mhz 640 MB RAM OS X 10.4.11 (iKey not active when launching Spark)  
(Version 3.0b9)

JMAX  One of the most useful - or even essential - Mac utilities on my computer(s). I'm amazed this isn't wildly popular and that Apple hasn't bought the company.

Use it to make the Control key + almost anything into a hotkey for anything! And if you have the Apple extended keyboard (a great item itself), use its 7 extra F keys with Control, Option and Command for 28 hotkeys before you even touch the rest of they keyboard.

Examples for one-touch hotkeys on my Macs:

Mail, Firefox, Photoshop, Lightroom, iTunes, Word

And not just apps: One touch: Applications, Home Folder, Downloads, WhooHoo!

I LOVE this thing!  
(Version 3.0b9)

JAZZADDICT  Spark disk image will not mount...  
(Version 3.0b9)

DANA SUTTON  I only have one criticism of this app. It should have available from the very first day OSX came out. since, like such other features as the old Apple Menu, managing F-keys was a feature of OS9 that Apple was wrong to deep-six in OSX. So when users upgraded to OSX they found they had to pay money to third-party developers to retain functions they had previously enjoyed for free. Now at last we have a free solution. Thankyouthankyouthankyou!!  
(Version 3.0b9)

ASMEURER  This won't accept Control-Spacae as a shortcut. I am trying to dump Quicksilver triggers for iTunes as they are kind of shaky, but I want to keep my shortcuts.   
(Version 3.0b8)

PJOT  Pure gold!  
(Version 3.0b8)

ANGELPLASMA  So good. Simple, elegant, and intuitive. App shortcuts, iTunes integration (with configureable track info display!), System controls, text macros... It's all right there. Love it. I'd definitely pay money for this (but I ain't complainin that it's free right now!)  
(Version 3.0b8)