Here is what I do in a smaller space (approx 60" x 60"):
Inner loop of Fastrack O-36 running a Lionel handcar (Frosty and Santa Claus)
Middle loop of O-48 runnind a 5 car Lionel Polar Expess
Outer loop of O-60 running an MTH Premier Pioneer Zephyr (yes, the gauge is too tight)