The following are the guidelines that I have been using to design my Lynnsport & Eastern layout.  I do realized that in many cases these are more blinders than constraints.  But I accept them as they are.  

What has worked for you?

Rule #1 - Yes, THAT Rule #1.

Rule #2 - I want to get a layout up and running quickly, and by running I mean trains orbiting the room.  Some might get enjoyment from "completing" a section.  Me? I get enjoyment from having trains running.

• Corollary 2A - Single deck only.
• Corollary 2B - Phased building is expected but modular construction is not seen as an option.  (Main line should be laid first with all needed turnouts off of it.  Then towns & yards can be added later.)

Rule #3 - I'm cheap.  More correctly, my funds are limited and I want to spend those funds on what is needed to get the trains running sooner.

• Corollary 3A - Powered switches are a waste of money (and time) when finger throw Peco switches work just as well.
• Corollary 3B - There is no need for train or car detection.
• Corollary 3C - But A&B not withstanding, there is no reason not to make advanced provision during construction for adding powered turnouts and track detection so it doesn't cost more in money and time with available resources change.  (Drill actuator holes, make sure there is plenty of wire that is easily disconnected to add track sensors, etc.)
• Corollary 3D - Wide benchwork requires more funds to finish, thus shelves should be no wider than necessary, about 14" or so.  There is no need to fill every sqare inch of space with track.  Less is more.  
• Corollary 3E - Avoid peninsulas as they take more lumber for legs, facia, and valance.

Rule #4 - I'm an N scaler, and that isn't going to change for the foreseeable future.  

Rule #5 - I am not a prototype modeler.  I am not a contest modeler.  I don't care about rivet counting.  I just want my layout to look "right" in my eyes.  Molded on grab irons are fine.  A slightly out of time car is OK.  Perhaps as the layout progresses I will add details.  But initially things will need to be "good enough".

• Corollary 5A - Atlas switch machines look like crap, but if they can't be seen, why not use them when you absolutely need a remote controlled turnout?
• Corollary 5B - I do not need to model a prototype railroad, nor do I want to spend the time searching for and research of a prototype.  Research is an enemy of Rule #2.
• Corollary 5C - The general aspects of prototype railroading should be followed to the extent that they don't interfere with Rules #2 & #3.  If I don't know how something was done back in the day, I will do basic research to make it plausible.  Note that "basic research" is the use of Google, Facebook, and MRH Forums.

Rule #6 - Frank Ellison is a God.  The Way Freight is King.  Railroads have been in decline since 1929.  So follow Frank and model the industry when it was at its height!

• Corollary 6A - No matter how cool, SD40-2's are banned.
• Corollary 6B - Switching is a must.
• Corollary 6C - Point to point operation is a must.
• Corollary 6D - The layout must connect to the rest of the world (even if it isn't in the world).
• Corollary 6E - The layout must support operating sessions.

Rule #7 - Design must be adequate to support NMRA AP certificates for Scenery, Civil Engineer, and Electrical Engineer.  (Chief Dispatcher is not necessary as I'm already close from operating on a friend's layout.)

Rule #8 - The Enabler must be happy at all times.

• Corollary 8A - My railroad room is what it is.  The walls are fixed and may not be altered or pierced.  Doesn't mater how easy you say it is to modify the walls and later restore them, The Enabler doesn't care what you say,  and that isn't a hill I'm willing to die on.  The room is about 10'x12'. I can use the closet on the one end for extra space, and I can spill a little bit out of the room on the other.  But not too much as that is my office area and I don't want to be cramped between my desk and my layout.  I do need to maintain access to the windows.  A removeable section across the entry way is acceptable.