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Generally no, but enabling Going Viral for any mission that didn't come with that DLC can considerably increase the difficulty of the scenario due to disease outbreaks. You may also want to avoid enabling Lobbyistico and the Llama of Wall Street since Lobbyistico's 'Corruption' mechanics penalize playing with the Swiss money / Broker side of the game to the point that it's rarely worth engaging with them while the Llama of Wall Street introduces market fluctuations that can make getting your economy up and running more difficult, especially early on when you don't have a lot of choice in what you export and having the price of a key export like Rum collapse can severely impact your revenues.
Other than that, the DLCs mostly don't actually do anything that significantly impacts the game, they just add some more industries or alternative housing options or other things like that.