I hold Tobirama accountable for the animosity felt by the Uchiha Clan towards the leaders of Konoah which subsequently led to their planned Coup D'etat and later annihilation.
Its seems too convenient to forget that the Uchiha Clan of the Leaf initially turned their backs on Madara and followed Hashirama. Tobirama from the very beginning disliked the Uchiha and even Madara acknowledged that the Uchihas were 'protected' and had integrated under the leadership of Hashirama, however he also warned that if Tobirama took over after Hashirama, the Uchihas would then be persecuted by him.
Although they were not out right persecuted, his fear of a revolt from the clan led to him isolating them, placing them predominantly as the police force of the Leaf, which in itself caused them to be resented by others (not to mention that the Prison was also placed within their already isolated area of residence which Tobirama had given them: on the outskirt of Konoah).
So yes, Tobirama was the reason the Uchihas harbored resentment towards the Leaf. If he had treated them as Hashirama once had, I feel it could have prevented the later annihilation of the Uchiha Clan. And Itachi would not have been burdened with the darker side of the Leaf; destroying his own Clan in order to save his brother (an innocent) from being murdered.