OK, placing most speakers on their side DOES change the way they sound to some degree. There are many factors at work here, the most glaring of which is the distance of the drivers from your ears and from the reflecting surfaces such as walls and the soundboard.
Distance equates to time of arrival. So let's say you are sitting at a mixing console with your monitors sitting sideways on top of the console. You have tweeters on the outside and the woofers on the inside. Draw a line from your ear to the woofer, and a line to the tweeter, and you can see that the tweeter is slightly farther away than the woofer! This causes problems in the region around the crossover point where the woofer and tweeter are both playing. Depending on frequency, this time difference effect can cause either a reinforcement of sound or a phase cancellation! What you get is called a "comb filter" effect, which when graphed on a frequency response chart looks something like this...
----/\/\/\/\-------
20Hz--------20K
Some freqencies boosted, some cancelled...
OK, that's just what's happening with the direct sound to your ear. Now consider the reflections you hear! The walls to the side of the speakers see the opposite time difference that your ears hear with the direct sound! Since the tweeter is closer to the wall than the woofer, there is a comb filter effect that is bouncing off the wall and diffusing into the room as reflected sound. This all combines into the total sound you hear and may have adverse effects.
There are some other reasons too, but they are a bit more esoteric.
Now, standing your speakers upright won't cure all this, as you still have ceiling reflactions and whatnot, but vertical is usually the best arrangement, as it avoids the most glaring issues.
Placing them on their sides may actually sound good in some cases, so if that's true in your case, go with it!
LooneyTunez is right on about the center channels BTW. An MTM arrangement (Midrange/Tweeter/Midrange) should NEVER EVER be place sideways! This type of speaker design is polarized vertically intentionally, and placing it on it's side for aesthetic reasons is acoustically hideous!