東京に桜が咲いています will be sakura is blooming in Tokyo. 東京は桜が咲いています will be Tokyo is blooming sakura.
東京で桜は咲いています 東京では桜が咲いています The は depends if you want make Tokyo the theme or not of your sentences. You are talking about Tokyo, or you are talking about Sakura. Yes, it is a very thin different nuance, but it depends from the context and from the nuance you want to do.
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東京に桜が咲いています will be sakura is blooming in Tokyo. 東京は桜が咲いています will be Tokyo is blooming sakura.
東京で桜は咲いています
東京では桜が咲いています
The は depends if you want make Tokyo the theme or not of your sentences. You are talking about Tokyo, or you are talking about Sakura. Yes, it is a very thin different nuance, but it depends from the context and from the nuance you want to do.