Yes there might be issues with relative pathing (….... stuff).
symlinks should make this transparent. As far as UE4 is concerned, its for Epic Games\4.6 and its getting 4.6 (Not E:\4.6 as in example).
Also last option, windows does let you mount an entire hard drive partition onto a directory. Just un-assign drive letter of that partition and mount it on directory. Inside Disk Management. (same right click absolute lower left on Win 8.1)
