Sometimes, clothing the plot of one kind of story in the tone of a different and contrasting kind of story can produce startling and unusual effects that give pleasure to the reader. Other times . . . well, at other times, the reader is more likely to conclude that the writer was trying to be clever, and failing. This tends to make the reader unhappy. (See John Scalzi on the failure mode of clever.)
This was brought home to me when I watched the 2009 film Duplicity, a complexly-plotted movie about corporate espionage and double-dealing which left me sufficiently disgruntled that I spent most of a long drive home from the movie theater trying to figure out what had gone wrong. My ultimate conclusion, at least as far as my own disgruntlement was concerned, was that the tone and the plot of the film didn’t match. The tone was romantic comedy with a side order of intrigue, while the plot more properly belonged to a Cold War era spy thriller in the Le Carre or Deighton mode — the sort of film that gets shot with a monochrome filter and you count it a win if anybody even vaguely likeable is still alive when the credits roll.
The proper ending for a romantic comedy/caper flick is for the sympathetic characters to finish it up drinking champagne and eating strawberries and chocolate in bed on high-thread-count sheets in a luxury hotel someplace with no extradition treaties. Nothing else counts as a win. With a Cold War spy thriller, just having the sympathetic characters (if there even are any) come out of things alive at the finish is enough to keep it from being a stone downer, and alive-and-together is enough to count as a win.
Similarly, the reader of a Cold War thriller will accept betrayals and skullduggery and sympathetic people doing morally-ambiguous things because the fate of nations is at stake — if things go wrong enough, it won’t just be a few people sold out and bleeding, it’ll be whole armies of them, and civilians as well. The reader of a romantic comedy is unlikely to be as accepting.
(Does this mean you should never play mix-and-match with tone and plot? No. It means that if you’re going to do it, be certain you can carry it off — and keep in mind the consequences of the failure mode.)