If you require open spaces for doodling or free-form brainstorming, select an unlined notebook; if you plan to render complex architectural or design drawings or do math calculations, you may benefit from a graph-paper notebook instead.
Choose a personal "look" for the interior of your Moleskine before you start to write. Use a consistent lettering style (e.g. all caps, cursive or printed letters) and ink color, and use a ballpoint pen, such as Uniball brand, or a felt-tipped pen. The interior of the notebook will then match its chic external appearance and won't have the dents in the pages that a cheap pen might leave.
Organize your notebooks with a table of contents and volume names or numbers. If you have purchased a number of Moleskines in your life, you may have problems finding particulars notes. Color-code the outside of the Moleskines using permanent markers to indicate the year, or use sticky labels to indicate the contents on the spine. Number your Moleskine pages and leave the first pages of each book blank initially so you can list the contents as they are added. Thus, instead of having to flip through twelve different diaries, you can simply check the table of contents of each one to quickly skip to the page you desire.
Be consistent about recording the same type of information in a consistent place on the page; that way you will be able to use your Moleskine as an quick and easy reference tool.
A final tip: Be careful not to overload the secret back pocket, as over time this could cause a tear.