GNOME 3 and Ubuntu's soon-to-be released Unity are the first GNOME desktops designed from the start with usability principles in mind. Not that releases in the GNOME 2 series ignored usability, but in GNOME 2, usability was an addition to the desktop, comparable to adding the foundation after the house was built.
Whether you use GNOME 3 or Unity will probably depend on your distribution's choice. But assuming you have a choice, which should you use? Suggesting an answer is hard, because in many ways the two are distinctly similar in design, with the differences largely in the details.
Which you prefer will have little to do with the applications available. Contrary to what some imagine, both are shells -- different interfaces that interact with mostly the same GNOME backend and applications. A few utilities, like Unity's Main Menu editor, are specific to the shell being used, but most of the software will be the same regardless of the interface with which you interact with it.
Similarly, because both are informed by recent design principles -- and possibly influenced by each other, since they were designed at the same time -- the look and organization of GNOME 3 and Unity is often surprisingly similar. In particular, both have more in common with the interfaces for music players and phones than with desktops for workstations.
Among other things, that means more clicking and changes of screens or windows in either than in a workstation desktop. Moreover, while both allow you to customize details such as the background color, options that affect work flows are generally rarer -- both, for example, assume that users will rely on menus for starting applications.
Although you can sometimes enable deprecated work flows, you will generally need expert advice or the patience to search many layers below the main desktop to find the controls that you need.
Given these similarities, don't be surprised if at first Unity and GNOME 3 seem almost identical. However, as you work with them, the differences do start to emerge fairly quickly.
The largest difference between the two interfaces is that GNOME 3 uses a minimum of two screens: one in which open windows displays, and the overview in which the system is configured and applications chosen and run.
By contrast, Unity remains oriented towards a single screen unless you use virtual workspaces. For light usage, this setup is less confusing and tiresome; in GNOME 3, it can sometimes seems like you are changing screens every few seconds. However, on a netbook in particular, Unity opens many windows full-screen -- or near enough to make no difference. If you work with more than a couple of windows open at the same time, the effect is not much different than working in GNOME 3.
Where most people are likely to notice the differences between GNOME 3 and Unity is in their implementation of similar features.
For example, if you add applets to your desktop's panel, or application launchers to your desktop, one of the first things you will notice in both Unity and GNOME 3 is the difference in work flows. GNOME 3 does not include the option of icons at all, and, while Unity does allow desktop icons, its design steers users away from them. Both interfaces feature uncustomizable panels with little on them except a clock and a collection of app indicators -- that is, controls for sound, batteries, Internet connections, and personal information. GNOME 3 also uses the panel for a task indicator.
GNOME 3 and Unity also eliminate the traditional drop-down menu. Considering that almost all monitors these days are wide-screen, with more horizontal than vertical space, this decision seems logical, especially for interfaces that might be used on netbooks. Instead, both add a panel on the left side of the screen, often referred to as the dashboard in GNOME 3, and as the launcher in Unity. But, whatever the name, this new feature displays basic and running applications.
Of the two, Unity's launcher is the most flexible. Since GNOME 3's dashboard displays on a separate screen no applications run on this screen it does not need to auto-hide when a window needs its space, and in its current incarnation it is mostly uncustomizable. GNOME 3's dashboard also has the problem of shrinking to near illegibility if you open too many apps, forcing you to fall back on the mouseover help to identify the icons.
In contrast, you can customize some of the icons on Unity's launcher. The launcher also accommodates large numbers of open windows by showing a collapsed view at the bottom that opens quickly when you need to scan them. Unity's launcher also replaces a task indicator with small arrows to mark open applications. Although these arrows are easy to miss at first, they are an elegantly economical use of space once you are aware of them.