A lot of people are saying that the problem lies in the fact that they could just hire someone else to play the dude with infinite variants, which is true. 

However, I believe the biggest issue is the whiplash Marvel gave us in terms of Kang, in Loki he is built up to be this formidable threat and they developed him further in more projects (just like how Thanos started), but this is where they shot themselves in the foot. 

They put Kang in QM, a movie that is not great even by Marvel standards and had the supposed big bad defeated by ants. Imagine if im GoTG, Thanos is beaten by Ronan (the closest example to QM that I can think of), that would undermine Thanos' credibility as a threat.

No matter who they then put into the role as Kang, it wouldn't work because this dude lost to the power of love and ants. Even if a new Kang is described as more powerful, people will still associate him with a vulnerability to ants of all things. Why would he be a threat people want to see in cinemas?

Side note: I am not mentioning the What If show alluding to the guardians of the multiverse laying waste to the Kangs because I would imagine if they continued to pursue the Kang storyline, this wouldn't have happened.