Balsamiq Mockups for Desktop from Balsamic Studios LLC is a simple, easy to use tool for creating UI mockups with a hand-drawn look to them. Balsamiq is a Micro ISV founded by Giacomo Guilizzoni, formerly a Senior Software Engineering Lead for Adobe. Mockups for Desktop is an Adobe AIR application with a small footprint. It includes over 60 UI element template that users can tweak to meet their layout needs. Resulting drawings convey the designer’s vision without being tied to the look-and-feel of a particular application platform or OS. Designs can be exported to PNG to share/review your mockups with colleagues. At $79 for a single user license, it is also a very affordable design tool.
Here is a basic Outlook-style UI created in only a few minutes with Mockups for Desktop.