There were some interesting stats around how different hand-held devices are more likely to be used in portrait or landscape mode. However it works out, the real estate you have to utilise is fundamentally structured differently in each case, and so is a prime candidate to take a more considered approach to your images.

In this example, I'm making different image requests depending on device orientation. In this case it is an image of a Nexus 7 in use, so when I view the demo on my Nexus 7 things get a bit Inception-like :-) ).
You can also experiment with this behaviour in-browser, by adjusting the browser size such that the aspect-ratio changes.

srcset="landscape_variant.jpg" media="(min-width: 400px) and (orientation: landscape)" srcset="portrait_variant.jpg" media="(min-width: 400px) and (orientation: portrait)"
View source of the demo for further details

Demo: Device Orientation (Inception)