Your horizontal layout does not make it instantly obvious which labels associate with which boxes. Are the checkboxes labeled to the right or to the left? (Yes, you can figure this out after a moment's examination. No, this doesn't make it a good UI.)
The vertical layout is less ambiguous.
I also want to address another part of your question:
...placing them vertically makes them seem too related to each other (reminiscent of a "select all that apply").
If the boxes are not related, I would expect them to have labels (text) that explain them in enough detail to fully understand the purpose. For example, "Yes, please send me promotional emails and special offers."
In your horizontal layout, there is no space for such a label.
I am racking my brains and I can't think of a scenario where completely disrelated checkboxes could be appropriately labeled with labels so short they will fit horizontally.
Also note one further option, if each checkbox is entirely disrelated. If the checkboxes each stand for the answer to a yes/no question, as in some legal forms, it could be more appropriate to use yes/no radio buttons with neither one selected by default, such that the user must actively choose one—rather than interpreting an empty checkbox (no action) as the answer "No."