This one's a little tough. Ensure and Insure are so close in meaning that some definitions seem to list them as synonyms. But others, not quite. There seems to be a slight difference, at least in tone. If I had to explain it, I'd say that the significant difference seems to be:
When you use it with an E, you mean you're taking an active role in preventing harm, loss, or damage from occurring. An ounce of prevention.
When you use it with an I, you mean you're agreeing to documentation stating that should harm, loss, or damage occur, you will be compensated for it. A pound of cure.
I've been seeing them used interchangeably a lot lately, and it could be that the meanings are shifting, and one day we won't have both spellings anymore. But I don't think we're there just yet, and I guess I'm here advocating for their uniqueness. Like a sentimental schmuck.