I'm in the process of testing a clone of my production site, which I have updated from 3.17 to 4.2. The two are running in parallel on the same machine / web server /database server.
First the good news: rebuilds are about 400% faster. A full rebuild of our largest blog has gone from over 50 minutes to around 14.
Now the bad news: interactive processes are about 400% slower. For example, the delay between clicking New Entry (or Write entry) and the Create Entry screen appearing, has gone from about 2 seconds to 8 or more, and other interactive process are equally tardy by comparison with 3.17.
I would greatly appreciate any suggestions where I might try to find some improvements in the interactive processes. One thing that I plan on trying is an unload / delete / reload of the database tables, on the basis that the upgrade process probably made some bulk changes and the 4.2 tables may be somewhat less than optimized as a result.
Reported on Movable Type 4.2

I am having the same issue after upgrading from 4.13 to 4.21. Rebuilds a lot faster, but anything that has to do w/.cgi files -- especially in the admin screens -- is very slow. When I click on a link I'm waiting at least 10 seconds before anything starts to happen.
Which hosting provider are you using? I'm experiencing similar issues on my Media Temple DV server.