Excel 365 is UNUSABLE for professional work — performance has catastrophically degraded

You've included a lot of good details and have tried quite a few solutions already.

One thing you have not yet included is a typical sample workbook with anonymized data. I understand you may not want to upload a workbook with confidential information and anonymizing the data can be a chore.  My suggestion: run Inquire's Workbook Analysis to audit a workbook and share the .xlsx here.  This will provide an extensive report about the workbook but not include the data.

— Moving a simple shape (a circled number annotation) across a worksheet takes SECONDS. This is not a complex object. It is a circle with a number in it.

— Scrolling is laggy and jerky, even on sheets with minimal data.

— Pressing ALT to activate ribbon shortcuts has a delay so severe that subsequent keystrokes are DROPPED. I have to sit and wait for your UI to catch up before I can use keyboard shortcuts I've relied on for over a decade.

— Selecting and editing cells is noticeably slower than it was two years ago.

— Interacting with comments is painfully slow.

— Chart objects are sluggish to select, move, or resize.

These are classic rendering issues.  Others have already suggested checking the selection pane for object count (or use the immediate window).  The entire workbook can be combed to check this pane for each sheet.  It only takes 1 sheet with a few thousand objects to slow the navigation.

I do use OFFSET, INDEX/MATCH, among others.

OFFSET is best avoided in 365 because there are better options.  INDEX/MATCH can usually be done with XLOOKUP.  A full audit of a workbook with Inquire will list all the formulas in a workbook and give us an idea of how your workbook is setup.