Having the right speaker set-up is just as important as the number of speakers. Without the right speaker positioning and orientation, the sweet spot of the sound could be lost. The most important thing to remember is symmetry. Always have the speakers at the same height, preferably ear height (except for the sub which doesn't matter), and always have each corresponding speaker the same distance from its respective ear. The subwoofer sound is too low for human ears to be able to position, so the position of the subwoofer can be anywere. The subwoofer is usually placed infront, were it is loudest.

2 Stereo Speakers (with or without Subwoofer)
The optimum positioning for stereo speakers are in a equilateral triangle formation. This means that there is an equal distance between the two speakers, and between each of the two speakers and you. There should be speakers off to 30 degrees to each side.

4 Speakers (Quad and 4.1)
This is the most set-up for high end gaming. Most newer gaming soundcards are capable of quad output, and are able to inexpensivily use two pairs of speakers for a gaming solution. The correct orientation for this is in a square pattern with the sweet spot in the direct center. The speakers can either face each other like in the diagram below, or they all can face the center. It is up to the user's preference.

5 Speakers (Dolby Digital 5.1, AC-3, Dolby Pro Logic)
This is the high end home theatre solution. There are many ways to set up this configuration, the most popular is in the diagram below. The two front speakers, L and R, are orientated so that they are 45 degrees apart, that is 22.5 degrees to each side. The front speakers could all be orientated forward, like the center speaker is, and the rear speakers can be angled.

Analog To Digital | 3D Sound Formats | 3D Sound APIs | Speaker Set-Ups