In Chrome you can open the responsive design mode with a click of a button in the web inspector toolbar. It's one of the few buttons in those developer tool bars I use constantly. Currently, in Safari you have to access this feature via a dropdown in the main menu. Would love to see it eventually added as a button to the developer tool bar. (Or ideally being able to customize that developer toolbar like you can the Webkit/Safari toolbar at the top of the browser someday, which is something that cannot be done in Safari/Webkit nor Chrome.) To note, in Safari Web Preview there is no keyboard shortcut for the Responsive Design Mode, but in Nightly so imagine that will eventually make its way to Safari which will help though a dedicated button would be great.
<rdar://problem/33223847>