Keep your layout simple
Optimize for most frequent resolution
Define the break points
Make a flexible layout
Make pictures to behave
Include Maximize and Minimize
Use media queries
Do you have any particular framework or library that you use for responsive design? I've been using Bootstrap, but there's only so much that it offers in the way of design and there's always a feeling there's something more specialized out there.
You have a good base layout here.
I don't think keeping your layout simple really plays a big role in large screens, but adapting your content rather for smaller screens is the must.
Resolutions are changing constantly with all the different size gadgets coming out, so what I have found works best is to leave a feedback page available to get the device and screen size which the person having an issue is using.
I personally don't use any frameworks any more as the are full of clutter and slow you down when you have to cut stuff out of it. I build a website from the ground up and starting from the smallest resolution. I keep the content in mind from the beginning and then structure it to each device screen size.
Using fluid widths instead of pixel based widths is a must as it makes your design flow much smoother. Using large scale images works better for responsive design as you have great resolution.
I find by building the whole website from scratch, I can make the websites exactly to mine and my customers tastes while being fully in control and knowing my own structure intimately.
Hope this helps,