What do you need done? If you don't need to go back and redo something, just work with the simplied sequence. But you can go back and work on the non-simplified one at need.
And there are times, such as simplifying a sequence to send say to the colorist, where you'd simplify and use that simplified sequence to create the additional XML/EDL/AAF and exported H.264 'comparison' file from the simplified sequence. Deliver that to the colorist.
But still keep working the project in the 'full' non-simplified one.