The principle problem for me is that Mathematica V12.1 does not work on the Microsoft 7 OS, although WRI claims that both V12.0 and V12.1 work on that platform. (Version 12.0 does work.) The problem is that notebook sizes and font display are altered so greatly (like the Option Inspector display is altered so much that it stretches over more than two 25" monitors!) that it is simply unusable. WRI did attempt to fix it, first by giving me suggestions for making system changes, none of which worked, and then with an hour and half Zoom session which was not able to fix the basic problem.
I first used Mathematica in 1996, just before Version 3 appeared. I liked the idea of a notebook interface. After some time it seemed to me that Mathematica notebooks were a fantastic new medium for development, communication and publication. You can hand a reader not only static information but also active calculation and dynamic displays. Such documents have much higher integrity than static printed documents. It is still possible to make mistakes, but not nearly as easy. Calculating or plotting from an expression is a kind of "proofreading". No error occurs from copying a result to a printed document. It is already in the document.
Unfortunately, this has not worked out nor made much of an impact. Exchange of information by users through the notebook medium is entirely through a few Mathematica aficionados. There is no detectable publication through this medium at all, despite attributes that should make it superior to pdf files or printed papers by orders of magnitude. Why doesn't the Mathematica notebook medium dominate technical publishing?
One reason is that this is a new medium with new attributes. (30 or 40 years is nothing in adapting to such a medium!) With every single approach that has style, smoothness and elegance, there are a hundred ways to produce cutesy drivel that descends to "computer junk" as Edward Tufte might say. It takes time, experience, usage, critical evaluation and communication. One important consideration is how much effort is required from the writer and from the reader to use a feature.
References and numbered equations are a feature of printed papers that must go back at least 200 years. Wolfram dutifully incorporated them into notebooks. But they copy the original and fail to take advantage of the medium. Try to use Find to locate an automatically numbered equation. When accessing a reference or equation, don't transfer the reader to another part of the document and then (maybe) provide some way to get back. Rather, bring the information to the reader at the place he is and where he wants to use it. So we might for convenience still provide a list of references at the end of a notebook but references in the text would not be numbers or links but Openers or Tooltips or Buttons opening a window with the reference.
Accessory information may include many things besides numbered equations. How about definitions, theorems, graphics, dynamic displays, sets of axioms? These might be in an Association in a crib sheet palette. The crib sheet might contain paste buttons for common routines used in the notebook and links to their documentation and also a dropdown Keys menu for the Association. Mathematica has thousands of routines but if there are a dozen rather specialized routines used in a notebook then this is a great convenience to the reader. It's building on intrinsic attributes and assembling selected resources for a restricted application.
A major shortcoming of Mathematica is Wolfram's penchant for supplying routines whose specification is top-down without providing bottom-up alternatives using basic primitives. Many of these routines involve graphical displays, to which WRI adds cutesy features with hidden code. They may provide varied forms but often not the form one wants and then the writer is stuck. If "everything in Mathematica is an expression" (not true) then why not "everything in graphics is a graphic primitive"? Then WRI could provide common routines with top-level specifications without the writer being trapped in them.
Another problem with Mathematica is the proliferation of Styles and Fonts that go with various constructs. Many of these Styles are deep in the Core stylesheet and may be difficult to find. I especially object to the graying out of various types of information. For example unit Quantities are displayed in Gray. Why? If these are the result of a year's experimental work and the chief result why are they in Gray when everything leading up to them is in black? Does the Physical Review print units in Gray? If one goes to the Core style sheet (and has one's own style sheet) one can change it but how many writers will know how to do that? Similarly for the pinking out of an Inactive expression. The Inactive and Inactivate routines are very nice. They give an additional way to present step-by-step evaluations and derivations, which I like to do. But they should look like regular expressions and not be pinked out. It has a Tooltip that indicates an Inactive expression; it doesn't need a second indication.
The entire FrontEnd gives the appearance of being a succession of ad hoc additions held together with rubber bands and scotch-tape.
The documentation facilities for application writers are just barely usable. The documentation for it is skimpy beyond compare. It still uses the old Workbench 3.0. I've worked with two other applications authors who tried to do documentation but gave up because they couldn't make it work. What is needed for writers is not necessarily in sync with WRI's documentation needs. Wolfram takes no interest or notice of what would be convenient for them. Workbench might be useful for WRI development but why couldn't a separate, cleaner, more transparent and better documented application be provided for those who just want to do documentation of their own applications?
Applications, as opposed to a simple package, are a powerful form of the new medium but most users are barely aware of them.
Mathematica has many nice features as well as many undesirable ones but for me the dream of a new medium sits like a neglected step-child in some dusty corner while Mathematica itself lies in shambles on the floor.
"Writers shouldn't have to become system programmers and experts in type setting to make their notebooks look good."
I don't agree with your expectation that manufacturers should support an operating system that has been superseded twice in the last 7 years, hasn't received much more than a security patch in the last 5, and has been completely unsupported in the U.S. since Jan. 20.
I am a new user of Mathematica and have zero problems formatting my text and computational notebooks from the drop-down Format menu.
It doesn't help me much. I'm thinking of buying a new computer (but the old one is still working great after 10 years!) Martijn's post makes me worry that a new computer will not completely eliminate the problem.
One of the problems with fonts is that different fonts can display with quite different sizes even if they have the same FontSize specification.
I wonder how many different fonts and font Styles are used by WRI in Mathematica? Their entire display quality might be more stable if they restricted themselves to a small set of fonts that displayed with a uniform size, with the same FontSize specification, and standardized their use over versions. If a user writes style sheets and uses other fonts then he's responsible.
There's no reason for WRI to use a different font just because they can. Writers shouldn't have to become system programmers and experts in type setting to make their notebooks look good.
Is the answer by martijn Froeling in https://community.wolfram.com/groups/-/m/t/1947038 of any use in remedying the font issue for you?
My original title to this posting was "The Problem with Mathematica" not "The Problem with Mathematica V12.1". My discussion covers many issues that predate V12.1. That was just the straw that broke the camel's back.
I am a heavy user of Mathematica, and I keep working with 12.0, because 12.1 is unusable for what I do:
1) my favourite keyboard shortcuts don't work any more in 12.1;
2) my collections of Manipulate panels behave erratically in 12.1;
3) with 12.1 I cannot export Graphics3D to vector pdf any more; I wonder if the PostScript engineer at Wolfram has retired and the position canceled.
I had been excited at the Presenter notebooks with scalable fonts. My impression is that the functionality has been abandoned half-done. To make a plot that scales in every detail is possible, but very time-consuming. I have not found a way to make the Tooltips and the Manipulate interface elements to scale with the screen.
I repeat, I love Mathematica, but I also have complaints.
I read your frustration and I agree on the Gray font for Quantities. Out of curiosity, why do you still use Windows 7?
I think with Windows 10 the situation will improve.