As a builder myself, I personally find the inner structure of a MOC the hardest part of the build. Normally, I can find the right pieces and use a good technique to achieve an accurate and aesthetic exterior, but often I struggle to but those exterior panels together. Technic is of course you friend, as this not only provides support but allows you to use various techniques such as SNOT.
Some advice I got from a Q&A in February with Koen from Flickr is to use the biggest parts I can find. He also recommends using bricks instead of plates, as they fill up more space and like bigger bricks, can hold more weight. These bigger pieces will help keep your internal structure strong.
Another tip he gave me us to use different coloured bricks in the inner structure. Of course you would use the colour palette of the model for the exterior, but if you use bright colours for the structure such as red and blue, they are easy to distinguish, and therefore easy to keep track of the pieces you are using. Different coloured pieces are also used in official LEGO sets so that the pieces are easy to identify, especially for children, instead of the whole set being full of just grey bricks.
If you want to check out the full Q&A you can follow this link: https://www.facebook.com/tipsandbricks/posts/538361463198958
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