If you drop the honorifics all together, then you'll have the audience wondering what the people are saying at the end of each name.
Translations routinely dropped honorifics when I first got into watching anime. For awhile I didn't notice this because I couldn't pick out the honorific as something attached to names as opposed to just a common word, like the Japanese "is" or "the."
Once I did realize the honorifics had something to do with the names, I quickly worked out that some of them had English counterparts and some of them were expressing things English had no words for. So when the honorific was dropped, I just assumed that's because it was unnecessary for the translation.
Granted, these were official translations that shipped with printed inserts that had pages and pages of translator's notes, so I felt no need to mistrust the translation. I figured that when the honorific was dropped, once I knew what an honorific was, that it really just didn't mean anything.
And, in fact, most of the time? -chan and -kun don't mean anything really important in most manga, anime, and other media. You really can just drop them most of the time.
Sometimes they are significant, but the easiest way to figure out when is by context. Ideally you watch the whole series before you TL and figure out if there's some plot point related to a changing honorific. Then you work out how you'll handle that.
With that said, how would you translate "san" or "sama" in a way that would make sense in English, then?
Well, this is my basic method.
1. Analyze the situation.
2. Figure out how an American writer likely would've treated that situation. Figure out if there are any American genre writing conceits that might apply.
3. Drop the honorific if it's expressing something typically expressed only by tone of voice in American English. (Expressing formality or other social constructs through word choice is simply not a very big part of English.)
4. If the honorific is expressing something that can be translated in some way, then figure out how to translate it.
If the series in question is using a fantasy or otherwise not-real-world setting, -sama can be turned into a fancy title (like Viscount or His Excellency) or simply Lord/Lady. In a real world setting, you may be able to turn-sama into a title appropriate to that particular character, like Chairman or President
If you can't, -sama is usually best dropped from subtitles and handled through pure acting in a dub track, since usually in anime and tokusatsu writing-- which use very unrealistic speech patterns-- it's just an exaggerated way of indicating how much a given character respects someone.
You can treat -san the same way in most contexts. If it's a fantasy setting, you can probably work out a title that would be useful as a -san equivalent. If it's a real-world setting, then have the characters do what their American counterparts would do if that makes any sense at all.
