1. If you are customizing the existing default template then DON’T forget to rename the default template folder so if at a later date the developer does a upgrade it doesn’t overwrite your design! This is the cardinal rule which many budding Magento designers overlook, it sounds very silly but trust me it happens with everybody!
2. Use static blocks for the navigation menu, don’t do hard-coding in the files, because your customer won’t be able to modify these files to add a small navigation item in the menu. It is best to keep things simple. And in case if your menu has both products and content pages, then it is worth to purchase a plugin which can accommodate both, it is best to invest in it rather then forcing your client to depend on you for ever or to learn coding! There are many plugins in the market which will enable the magento designer to accommodate category, subcategory, product, even images, videos and forms into the navigation menu! So try it out!
3. Look out for I.E-9.0 browser compatible issues, don’t forget to check specially the checkout page’s authorize.net’s fields as magento 1.5 has issues with it!
4. The default template of magento is already search engine friendly with h1, h2 tags in it, so don’t overwrite it accidentally if you are customizing that.
Almost everything is possible, so keep an eye open for the latest plugins available in the market and you can be sure of nailing the best design!