Okay... I know one thing: LaTeX2e isn't meant for manuscripts. It's good for getting good results on book formatting, but getting properly formatted manuscripts out is difficult. I'm playing with the manuscript formatting guidelines provided by SFWA.
First, LaTeX2e isn't fun for people who demand exact formatting. Exact as in "these margins". (Margins can be arranged... somewhat). Exact as in "that particular cover page". (Eh... this can almost be arranged.)
But the part where LaTeX2e seems to fail most spectacularly is "This particular font". Courier. Yeah, TeX has Courier. Everyone has Courier. But then these people want "these margins" and throw in "we want ragged right, too, good heavens, not justified".
The rubber raft gets squeaking violently. LaTeX2e handles Courier. It tries its best to do the margins. But if you try "ragged right and these margins and Courier too", weird stuff starts to happen.
Also, LaTeX2e makes it a bit non-straightforward to write new document styles, the easiest way seems to be \input my styles. Hmm...
So what the heck should I do?
I kept thinking of "hey, a low-tech solution: Toss LaTeX and try Troff." The problem with Troff being that I'm not at all familiar on where to get documentation. I hope the GNU Groff documentation is worth a try.
Second guess would be Lout. I used this typesetter a while ago on a game project, and it seemed just fine as long as your requirements were simple - and heck, manuscript formatting requirements are epitome of simplicity. Perhaps I could try that again...