President Lincoln was clear on wanting to send all freed slaves back to their home country. He had popular support for doing so as well. There's rly no way to even guess how that one decision would've changed things in America.

President Kennedy wanted to eliminate the Fed, dismantle the CIA and curtail America's involvement in Vietnam before it became an undeclared war. Obviously, Oswald had other ideas. But it's interesting to consider how just those three things would've massively impacted America.

Then again, the death of Archduke Ferdinand ultimately led to World War I. And World War I eventually led to World War II. And World War II led directly to the post-war order we have now. So, that's a pretty significant assassination too.