Keyboard shortcuts with a single key?
It is possible to do, both natively and easily. Mac OS X hints has a hint (also check Lri’s comment) on how to set up keyboard shortcuts from the command line. We can use this to create single-key shortcuts.

You’ll need to know the application’s bundle ID (unless you want to set global shortcuts, naturally). For special keys, @ is ⌘; ~ is ⌥; $ is ⇧; ^ is ctrl. You can also check other values.

I’ll use Tweetbot as an example, setting “New Tweet” to ⌥+N, and “Reply” (on the multi-shortcut example) to R.

For one-shortcut commands, you can use the form:

defaults write com.tapbots.TweetbotMac NSUserKeyEquivalents -dict-add "New Tweet" -string "~n"


For multi-shortcut commands, use the form:

defaults write com.tapbots.TweetbotMac NSUserKeyEquivalents '{
  "New Tweet"="~n";
  "Reply"="r";
}'


For system-wide shortcuts, use -g, instead of a bundle ID.