I'm reading a book on the spies working in
Elizabethan England and it occured to me, if Mary of Scotland had died earlier, without Elizabeth being implicated, it would alter late 16th century politics in several ways. If durring the escape from Loch Leven Castle Mary had caught a bad cold and said cold had turned into pneumonia, then from 1658 onwards, Catholic opposition to Elizabeth would lack a workable figure head.
Phillip wanted to rule England, but he never had the time to focus on conquest of England. It was only the international scandle of Mary's execution that pushed him to the Armada. Elizabeth's main horror in naming an heir, was a fear of assassination. Without Mary of Scotland around, few would pin the hopes of Catholic Europe one her son James. Elizabeth might easily be persauded to except him as an heir. It's also possible that, with reduced international tensions, Elizabeth might see marriage as a workable possibility.
It seems to me that once James is born, Mary of Scotland's death becomes useful to anyone who wants a strong stable England. I could see several different schemes by Centrum, the Cabal, nationist groups (both English and Scots, heck maybe even spainards trying to prevent the disgrace of the Armada), even Homeline, might see killing Mary of Scotland as a viable plan.
Mid-16th century Scotland is both alien and familiar, a great place to set a campaign. PCs could be guarding Mary or out to kill her or just making sure their side knows what really happened. All kinds of storyhooks are availible.