replace internal drive

If I replace the internal drive, using a USB external with a CCC or Time Machine backup for my new source drive, will I be able to start up all the apps (photoshop, lightroom, word, etc etc) without having to re-enter the application serial numbers? Also, should I use migration assistant?

Usually yes though Adobe stuff can be temperamental from time to time. I would suggest using CCC, SuperDuper or even recent editions of Disk Utility to make the clone. Time Machine on its own does not produce a bootable clone.

Once you have made the clone, and before erasing/getting rid of the original boot from it to make sure everything work. I once had a clone that would not take my password.

Thanks, sounds like good advice. So once I boot up from the external and check all, and then replace the internal drive with a new drive, do I use ccc again to again copy everything back to the internal drive?

Yes. Depending upon how much you have to copy it could be a bit time consuming but you can usually start the process and walk away for a while.

Unless the old drive is failing or you have other uses for it may I suggest keeping it around as a bootable backup is easy using either a drive adapter or external enclosure. With regular cloning to cloning to keep things current you could be back up and running in no time with little or no data loss.