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When selecting a layout, don't try to reinvent the wheel. The wheel is still around as it works! Choose a template or design that your clients and viewers are going to be used to having a look at. This builds visitor comfort and familiarity. Give it some thought. No-one wants to go to a fairly cool looking site which has no usability. If your customers and viewers can't navigate or read things clearly, it doesn't matter how chill your website looks!
If you're building a blog or just making modifications to it, remember that content is important. It is very easy to get caught up in the design and on page optimization aspect of the web and neglect the real 'meat' of the site - content. On page optimization and a clever design is going to help attract visitors to the site but it won't keep them there. A great web site is going to need to nail both sides of traffic generation. Design and Content.
So you've got your website done and you're ready to launch it? Wait. Before launch, test everything about the site. Look over absolutely everything that went into the design. Make sure the URLs are optimized. Check the site in different browsers. If you've got the opportunity, check the site from 2 machines with different operating systems. 2 of the most well liked internet browsers and Firefox and Internet Explorer. If your website is broken in Internet Explorer, you are going to alienate that portion of your viewers!
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