So I'm designing my track plan for my 8'x12' layout and am confused on if 4.5" is enough spacing from center rail to center rail I will include a file from SCARM to show my idea. That middle loop is a subway loop.
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Take your two longest cars/engines and push them around the corners,one on each track, to make sure that they don't touch each other at any time. Then switch them (inside car to the outside, outside car to the inside) and do it again.
Totally depends on your equipment, and the curve radius. We decided to go with 6" all the way using 072 and 080 curves because we have some 21" passenger cars and articulated engines with lots of over hang. If you run smaller equipment, 4.5" won't be a problem. You can all the way down to 3.5" spacing on straight tracks.... but you won't have any room for "high wides" 
As posted above, it depends on equipment.
Worst case I know of? A Big Boy and 21" passenger cars or a Schnabel car with transformer installed. Long with lots of overhang. If running both on side by side tracks 6" is needed at and near the corners.
If running both in the same train or not at all, not so much. You can get a bit extra by starting the inner curve a couple inches closer to the middle of the layout.
This lets you hold the 4.5 on the straight but go up to 6 on the curve. Easements make this work even better.
If using all sectional track, make the first curve section the largest curve made for that track, then step down to tighter radius. Mirror it to get the smooth look without weird angles and length to fix.
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