I hesitate to say "the biggest" because I am sure that there are other ones.
I felt that half of the proposals I read were just not clear. I know that's a vague requirement, and yes, clear to me is not clear to someone else.
But, nevertheless, I had to work to figure out what were these people proposing to do. Part of the problem in the writing, and perhaps the design/thinking was mixing up significance with design. Part of it was way too much Significance (3-5 pages of 12). Part of it was too much preliminary data (results all over the place, in every section, and repeated). I get that you have prelim data. But tell me what it means, succinctly and then move on.
After the big question (will bunnies hop?), what are the next level questions. This is what specific aims are supposed to do. But in some proposals they didn't.
Then, how are you going to do this?
What was the sample being used? What were the experimental treatments? What were the independent/carrier variables, the response/dependent variables? What other non-scientifically-relevant, but confounding variables were in the analysis? How did the results, in your response variables, test the hypothesis (as in "if we see X then we can conclude Y"). Heck, what are the specific hypotheses (or milestones) you propose to test. This is linking significance to design/approach.
One of the hardest things in writing a proposal is figuring out how much and what detail to include of the research design. I reviewed proposals that were making type I and type II errors on this: including stuff I didn't need, and failing to include stuff I really wanted or needed to know. I was wading through the wrong detail to find the right.
[oh, I appreciate that you have a complex outline scheme that goes down to III.b.1(a). But, those numbers are useless without some headings. I am not going to be deeply understanding of your particular and idiosyncratic numbering scheme, so that when I get to III.C.1.(a), I have no clue as to why it is in a new section. Short headings like "variables measured" and "statistical analysis" are very nice.]
But one signal (meta criterion) that these proposals had problems were that it was clear they were busting at the seams: small (5mm) margins, no extra space (even 6pt) btwn para, let alone sections, no indents for para, 7pt superscript citations, small figs & captions. It made me think that the PI didn't really know what to include and what to exclude and was trying to err on having everything there.
There are no easy rule of thumbs for "being clear in your writing". I read many proposals that were clear with all the things laid out and I could follow them. I could concentrate on reviewing the proposal for content, not on figuring out what that content is.
Here are a few ideas. NIH has tons of info for reviewers (I reviewed this a while back, and will put an update in another post). One thing to do give the proposal to a colleague who is not in the same lab, and ask them. And, are there sentences that says "The significance of this proposed project..." and "The innovation in this work lies in ..." and "If this project is successfully completed, we will change the world by making it safe for bunnies everywhere...".