When creating mojoPortal skins, I've found that the simplest thing to do is take an existing skin that has a layout you find attractive, then modify the heck out of it (colors, menu tabs, graphics, etc.) until it looks exactly the way you want. If you are trying to adapt something like a template from another type of CMS, you can again refer to delivered mojoPortal skins to find the CSS selectors to include and modify. I highly recommend the Firebug browser extension to inspect elements on the page. The css files you are looking for would probably be either stylemenu.css (for "legacy" type skins), or style.css for Artisteer skins.
Remember to set the following keys to false in your user.config, so that when you update css it is immediately reflected, and when you inspect the elements with Firebug you can see exactly which .css files need to be changed. Change these back to true when your skin work is complete.
<add key="CombineCSS" value="false" />
<add key="MinifyCSS" value="false" />
<add key="CacheCssOnServer" value="false"/>
<add key="CacheCssInBrowser" value="false"/>
Of course, if all else fails, you could invest in a copy of Artisteer to make the skinning a breeze (see the link in my profile to the left). I can personally vouch for this program. It has saved us a TON of work.
Jamie