Well, to be honest we're brought in after the fact in most cases... so I am hard pressed to call it 'the biggest mistake'. Sure, in a perfect world I'd love to be consulted as part of the initial business development...but that is rare.
To me the worst thing one can do (via DIY
SEO or in-house etc..) is hap-hazard link building.
Another common thing is peeps that come to us once they have tanked from the ranks. In most cases, 80%+ it is because of bad link building practices and the mighty G has given them the slap.
So for me, 'bad link buidling practices' are easily near the top if I had to list 'the biggest mistake'.
I can always work the onpage/onsite and build links... getting a site back from the dead... is a long and expensive process.