The irony of Fletcher raising the girls
When Fletcher was forced to leave Alice behind, that was very tragic and difficult for both of them, because all they wanted in life was to raise a family together. That's why it's ironic that when Alice dies, Fletcher ends up raising her kids. Even though everyone back home worked so hard to keep the star-crossed lovers apart, fate still allowed them to raise a family together, albeit in a broken, challenging way.
The irony of the sister's diverging fates
Faith and Hope seem like they should be best buddies. They shared their lives in England, they shared their difficult voyage to the Colonies, they shared their adjustment to their new lives, but in the end, one single moment changed their destinies forever. By the end of the novel, the two sisters literally need a translator in order to communicate, because Faith is so inundated with her life and identity as a Native, that she doesn't remember how to speak English.
The irony of war and peace
Ironically, it's exactly opposite of our human instincts to do what leads to peace. When Mononotto decides to do what is best for his family, he goes for the "eye for an eye" kind of justice, seeking retribution. Ironically, his attempt to bring peace to the pain of his son's murder ends up leading to even more death and catastrophe.
The irony of "witchcraft"
When Nelema decides to help the settler with the illness, she doesn't know how much it will cost her. Ironically, the villagers arrest her for witchcraft, even though her work was clearly medical in nature, because it really healed them. The villagers were so convinced that this Native American was clearly a "savage" that when she offered them technology they didn't know about, they automatically assumed she was working with demons. This irony underscores the main irony which is that, actually, the Native Americans were a legitimate form of government that should have been allowed to negotiate for themselves.
The irony of the sacrifice
The central irony of the novel is Mononotto's realization that his own thirst for revenge has led to more damage in his immediate family. This happens when Mononotto steals Everell as a recompense for the murder of his son, and he decides to kill Everell in a sacrifice to the gods. But the gods have a different plan, it seems, because he only ends up injuring his daughter who steps in to save Everell as an advocate for mercy. It seems that Mononotto accidentally did the exact opposite of his intentions.