Eddie,
I have an approximate 8 x 20 layout and run 1 loop of standard gauge and 3 loops of O gauge. I am running 72 inch radius Standard Gauge, with 1 straight section of track at the center of the curve, the a loop of 72 inch radius O gauge, a loop of 54 inch O gauge radius, and a loop of regular O gauge (whatever the standard radius is).
As far as the spacing goes, I did not do anything special for spacing and found that the tracks spaced out well based on their respective radius curves. I just checked the spacing at the front of the layout and I have about 5.5 inches between the loop of Standard and O gauge 72 inch radius and about 6 inches between the O gauge 72 inch and 54 inch radius. I get much more space between the rails on the curves. I did not check the spacing between the smaller radius and the 54 inch radius, but there is plenty of room there.
Here is a photo from just after the Standard Gauge, O-72 and O-54 track was installed.
Here is a photo with the smaller radius installed. I did it as a dog-bone type loop, going behind the large Union Station.
Another shot from above
NWL
