Do Mac installs become progressively more 'crufty' by using Migration Assistant? I'm on my sixth Mac since purchasing my first in 2006. I've used Migration Assistant on every upgrade. In between upgrades, I've installed and removed lots of programs, changed lots settings, added and removed stuff all over the file structure while programming and on other spelunking excursions.  My Mac still runs fine, but I suspect it may be a little disheveled. What's the best practice with Migration Assistance in cases like this?
You may get a lot of opinions about this but I have been migrating from one Mac to another since the original Mac O/S public beta with nary a problem.

On occasion I will make a quick pass through the root and user level Application Support folders and remove anything associated with an app I know has been removed. Same with the Preferences folder (both User and Root).

Utilities that show you file sizes so you can find disk space wasters are handy here as are utilities like CleanMyMac or Onyx to get rid of cache and other temporary files.

But my days of poring through the file system for stray files ended when I had more disk space on my Macs that I could ever possibly use, so I don't sweat the small stuff. Much of it takes up very little space and I have better things to do than manually remove a thousand (or more) preference/settings/support files.

If you have a Mac with limited disk space that may not apply. In that case keeping on top of the disk space used with cache cleaners and utilities to spot the largest files/folders are your best friends.

When buying a Mac I go with the old engineer's rule of thumb, "buy as much RAM and disk space as you can afford."