If you're submitting a hard copy of your application, a light-brown ring on the front page of the document where a coffee cup has been put will result in the applicant not even being considered: the CV will go straight in the bin. Likewise a soggy cornflake - and I've seen both.
Simple spelling mistakes imply illiteracy and/or carelessness, to say nothing of the self-evident inability to use a spelling-checker. Remember though that some of the more obscure punctuation errors might not be highlighted by your spelling checker - so get the whole thing proof-read at least once, and preferably twice. It might not be the done thing to criticise people openly for making grammatical errors these days, but that doesn't mean they aren't noticed - and when somebody has a limited amount of time to compile a shortlist of candidates for interview from a large pool of applicants, such errors can finish you.
As other posters have indicated, no more than two sides of A4. If there are a lot of applications, the shorter ones are likely to be read first. No fancy fonts, please.
If we're talking about a professional role, having an up-to-date entry on LinkedIn would be a good idea (in which case provide a link to it on your CV) - but if you do that, make sure what you tell them in your application tallies with it. If you've got your own website, provide a link to it - but only if the content is business-related. If you've got a Facebook page that's publicly accessible then they'll probably visit it, so make sure it doesn't contain anything at all that you wouldn't want them to see - especially not any derogatory remarks about your present employer.
Make sure you can satisfactorily explain any gaps in your career. This one really matters, because they'll be wary of applicants who have just served prison terms that they don't want to talk about.
If the interview is going to be held remotely because of COVID (e.g. via Skype or MS Teams), be prepared to be seen on camera. We had half a dozen candidates to interview recently that way: we didn't ask to see them visually because we felt it might be regarded as intrusive, given that they were probably calling in from their homes, but one volunteered. Her personality and confidence just shone through: she got the job.
Hope this helps