I'll assume that by 'design' you mean DTP.
It depends upon what you mean by 'popular'. If you mean 'well-liked' then Quark has, until recently, been the undisputed leader with DTP professionals. (Most newspapers and magazines have used this software for many years. Many continue to do so). Anyone who has ever used Quark knows that it's a superb program which is incredibly intuitive (so that beginners can get professional results in minutes) but it also offers fantastic extra facilities for advanced users.
In recent years, however, Quark has faced tough competition from Adobe's InDesign software. This is primarily because InDesign works so well alongside Adobe's other flagship program, Photoshop (which is definitely the best image manipulation program and provides the 'industry standard' within the publishing industry).
So, if you're looking for the 'most popular' DTP software, as defined by the professionals, the answer would probably still be Quark If you asked those who work in the newspaper industry but InDesign if you asked those who work in the advertising industry (where seamless integration with Photoshop is more important).
However, if your definition of 'most popular' simply means the software which is on most PCs, then you'd have to consider something like Serif's PagePlus SE. It's incredibly popular because it's free! :
http://www.freeserifsoftware.com/
Chris