Really, setting up spoeakers is a skill that takes a lot of knowledge, experience, skill and patience!...ESPECIALLY, wshen you're talking about multiples of speakers! If you don't want to do you homework, and want quick, finalized results, you are best hiring an expert to take care of the mater, plain and simple. Otherwise, you need to get all the literatuture you can gather on what to consider for setting up speakers, room acoustics, etc, and exeriment!
Speaker and seating placement in the room are the two greatest factors in the foundation for good sound acoustics wise. Your main goal should be finding a good balanced, reasonably flat response from each speaker in relation to your seating possition! However, symetry between all the speakers and seating possition, coupled with getting balanced, coherent sound from speaker to speaker, is A RATHER DIFFICULT chore, especially given most people relative incexperience with such matters, and also, NON SYMETRICAL ROOMS!(making balanced setups challenging...especially from multiple seats!)
By finding the right spots for each speaker, you're basically "EQ'ing" the speakers, and it should be done one speaker at a time!
Again, as the other gentleman (Sean) mentioned, you must take into consideration obstructions in the room, openings, windows, furniture, protruding and intruding structures, etc. ...and this is only for considring the FREQUENCY RESPONSE of the speakers!..I'm not even talking yet about reflection colorations at this point. If you can't set up a speaker to sound balanced in the bass/lower midrange, and not boomy, peaky, lean, thick, slow, etc, then the rest of the acoustic considerations, mean very little!
Next you should consider soundstage, tow in/tilt, etc. Finally, treat room reflection points, etc.
Again, more needs to be known about your room situation, indeed. Like, how high is your ceiling? How far back do you sit, and where exactly in the room (conidering the actuall room shape and such, which you didn't mention for the entire room, and more is needed) do you sit?!
Really, to be truthfull, there is no simple answers to your questions, with out more indepth detail about your room and set up. Also, unless you know what to listen for, or what a properly balanced speaker sounds like (although this doesn't take long once you know), or how to measure speakers, treat acoustics(whether using furniture or after market treatments), etc, there's just way too much to consider in thinking you're going to get truely pheonominal results on your own at this stage!
If you really are into doing this yourself(and be aware, that the majority of audio enthusiests end up with poor results on their own..just the way it is), then you need to start your studying, and start your experimenting...and I also suggest you invest in a sound level meter, a test tone CD, and a few acoustics books...not to mention reading all he back issues regarding room acoustics, speaker placement(rare indeed, trust me), bass response, etc.
In short, there's no replacment for experience, knowledge, skill, and desire/interest!(and you level of them all!).
Now I know that I can set up a seaker as good as or better than anyone, in any given room, but then you're talking with someone who's done over 1000 set-up's over the years, involving all kinds of rooms and equipment, and can honestly say that MOST people never get this part right, with ANY level of gear! Rooms are all so different, and so is gear, and they're usually quite small compared to large commercial rooms, which makes set-up and acoustics even more critical.
Anyway, good luck. If you really want to find out how to make things sound right, good, even world class, you must put in the time, and be willing to pay the price...or just pay someone.