Mail.app - Shortcut to switch signatures?
Sorry to dig up an old question, but I had the identical issue today and this was the first result for my google search for “mac mail signature shortcut”. While these answers weren’t what I was looking for, the 3rd google result was a MacWorld hint, which offered the perfect solution.

Here’s the answer: you can assign keyboard shortcuts for your email signatures, “From:” account selection, and even SMTP account from System Preferences → Keyboard → Keyboard Shortcuts → Application Shortcuts. To set up your shortcut, click the + icon, select “Mail.app” from the Application drop down, enter the text of the signature (or other option) as it appears in the New Message window drop down, and give it a keyboard shortcut. Rob Griffiths, the author of the MacWorld hint, advises using ⌃ (control) in combination with your desired keys to avoid conflicts with existing Mail shortcuts, which seems smart.

In my case, I created a shortcut in Mail.app for the menu title “None” (the first option under signatures) and assigned it the shortcut ⌃X. It is now exceedingly easy for me to clear my default email signature when it doesn’t seem appropriate.

For the purposes of illustration, here is the System Preferences → Keyboard Shortcuts pane (it’s the last item): 

And here is what it looks like in Mail’s New Message window: