Koch
I am quite sure you already know how to set up your machine considering you have been running mills for years and just hand coding.
All CAM will have different features and most Cam users will be able to do this in many different ways.
Initial part location is done by using a "set MCS" command which allows you to locate X0Y0 of your part (or stock block) with a few mouse clicks and maybe a number input. Then tell the Cam to output your FO number (G54, G55,...).
In the most basic software it is likely easiest to make separate programs. It is also possible to program the part as 4 or 5 axis and then hand code a M00 in between sequences to allow you to move the part. This can be dangerous because it requires the programmer to think a lot and add the right code in the right place (risk of error is high).
Cam will also allow you to flip/rotate the WCS between Mops which will work effectively the same as the 4/5axis scenario.
Maybe go to MecSoft.com and download their demo of VisualMill 6 and play with, it using the online tutorials.
www.integratedmechanical.ca