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In my past experiences, I have almost never typeset my manuscripts according to the formats required by the journals to which I would like to submit. I leave my manuscripts as produced by the LaTeX article documentclass.
Recently I am wondering: Would such a behavior generally give handling editors a negative first impression?
Speaking as both an editor and reviewer, I am definitely prejudiced against a paper that fails to follow prescribed submission formatting (which may or may not relate to the final published format). It is simply a matter of professionalism and prior correlation.
As an editor and reviewer, you see a wide range of material submitted. Some is really good, and some is really bad. I've even gotten a few that were outright insane. The vast majority of the papers that failed to follow prescribed formatting were definitely not good.
Making a good-faith effort to follow formatting requirements generally isn't hard to do, and especially when doing so just means using the journal's LaTeX package rather than the default. Neglecting it means that the author is being sloppy and unprofessional at something easy. This doesn't necessarily impugn their science, but if they don't care enough to follow professional standards on something easy, it's a good indicator that they are likely to be unprofessional in other places where it matters more as well.
One exception: I am likely to give a pass to particularly aged/emeritus types who have a solid track record but are clearly not comfortable with modern word processing technology.
I'll venture a minority opinion (I'm in mathematics, where the culture is very possibly different than in other fields).
As a referee, I have an instinctive negative reaction if I know that an author has taken the time and effort to conform to a particular journal's style. The grounds for this is that most journals employ typesetting staff for this purpose. Especially considering the very high price of many (if not all) journals, for authors to refuse to do this suggests to me a principled refusal to waste their time.
That said, I can see that many people hold the exact opposite opinion, and even that my own feelings may be a little bit silly. So I certainly don't actually hold this against authors when evaluating submissions. (Indeed, if I receive something formatted, I never know if it is the author or the editorial staff that has formatted it.)
My impression is that most (but maybe not all) mathematicians wouldn't hold it against you if you don't bother. Moreover I believe that most mathematicians in fact don't bother with such formatting guidelines.
I have never heard anyone voice @jakebeal's opinion before. Of course, counting the upvotes, he speaks for at least eight other people! You might take this as evidence that the answer to your question is dependent on what your field is.
Beware of what the journal styles put into your paper. For instance, Elsevier's style file elsart (recommended for instance by this journal in my field) contains a footer with the words "preprint submitted to Elsevier". If I haven't submitted it yet, I don't want to write a false statement on an e-print on arXiv. The recommended style file for this other journal in the same field inserts the text "Copyright © 2010 John Wiley & Sons, Ltd." on the manuscript, which is outright false and borderline criminal in my view.
So you'd better not use documents created with these classes for anything beyond journal submissions (e.g., preprints, which at least in maths are basically a necessary step, or sending manuscripts to a colleague). This means that if you use them you need to prepare at least a second version.
My experience is that changing LaTeX format can be time-consuming, due to various package incompatibilities. So I have started submitting papers using the style which I am already using for the preprint (and for my internal notes --- I typically start to write down a manuscript much before deciding to which journal I am sending it). No one has ever complained (editor, referees...). More recently, Elsevier explicitly authorized this practice on many journals by launching an initiative called Your paper Your way.
So my suggestion is just forget about journal styles unless someone insists on them.
What reason might there be for not using the journal's format? Here is the one I have heard of.
If your papers are always accepted by the first journal you send them to, then you might as well format them for the journal. (But it probably means you are aiming too low!)
On the other hand: if you sometimes have a paper rejected by one journal, then send to another (and another, and another...), why should you have to change the formatting for each one? In cases like this, the author would prefer to do the formatting once, for the accepting journal. Sensible journals would allow this.
Not surprisingly, the best way is to follow the instructions. But, if you for some reason do not then keeping a manuscript very simple is the best second approach. Simple, generic, typography, 1.5-2 line spacing, figures and tables separate from the text works in most cases. As an editor and reviewer I find evidence of special formatting most annoying. It distracts the reading and is also completely unnecessary since the journal will likely reformat the article during type-setting.
There are some aspects where you should try to put some effort in: try to make sure you adhere to the journal's standard fro referencing and make sure your reference format is correct. It is really annoying when references are not complete or the reference list is haphazardly put together. The key is in the details so make sure you get the details correct. You do not want the editor or reviewers to get annoyed by inconsistencies in details, make sure they can read a well prepared manuscript with little effort and disturbing elements.
So, if you cannot follow the exact instructions, just keep it very simple and avoid inconsistencies.
Sadly, many journal submission guidelines still request an archaic format in which the figures are all placed at the end of the manuscript. Often the figure captions are themselves separated from the figures. This may have made sense in the days of hard copy submissions, but is pointless -- especially at the review stage -- given current technology.
As a reviewer I find this format intensely annoying and it is possible that my review quality suffers as well; I sometimes read through several figure references before flipping back to look at several figures at once. My personal opinion is that authors' highest priority should be to submit their work in a format that minimizes effort on the part of the referees, and if this conflicts with house style requirements, the author has every reason to ignore those requirements.
This is not to promise that every journal will tolerate such a decision on the authors' part, but I have never seen a harsher consequence than a relatively polite request to reformat.
I think there's a balance to be struck here. Some reviewers will be annoyed if there's no room on a printed version to scribble their notes about the paper. This means that typical IEEE/ACM two-column, single-spaced formatting might annoy some people. The argument from them pretty weak if your formatting conforms to the journal style rather than being some tight format that you made up.
On the other hand, using the journal style generally gives you a reasonably readable presentation designed, more or less, that way. It was probably also designed in the age of print to get the most words on the page, so it's not perfect.
The worst thing you can do from a reviewer's perspective is to come up with your own formatting that looks slapdash, unprofessional, sloppy, or is hard to read. Almost no matter what you do, someone will be grumpy, but if you use the journal template, you'll engender the least complaints.
If you are writing your paper in LaTeX, then you should use the LaTeX template provided by the journal (I have yet to submit to a journal that does not provide a LaTeX template). This will take you a few extra minutes.
The LaTeX output is what both the editor and the reviewers will see. Why would you not want to ensure this looks professional? Are you submitting to so many conferences you do not have an extra 20 or 30 minutes to polish your submission?
I don't check for adherence to journal standards during reviews, but I've gotten several papers where the author(s) didn't see what the LaTeX file would look like in PDF form. These papers almost always have other issues, and reading through a poorly formatted PDF discourages me from giving the paper the extra attention it might need.
