Although there is no proverbial "smoking gun," odds favor the separatists' being responsible.
First, there was a purported social media post, but that post was deleted and its authenticity was not verified (at least not yet).
Second, Ukraine has been using air power, while the separatists lack air power. Therefore, the separatists would be more likely to be firing at planes than Ukraine.
The Ukrainian government has made claims about an intercepted conversation, but both Ukraine and the separatists have engaged in frequent disinformation, so that matter will need to be independently verified.
At the same time, it is possible and perhaps more likely than not that the BUK missile system had been seized at some point from Ukrainian forces. Reuters reported:
On June 29, Russian newswire ITAR-TASS quoted separatists in Donetsk in eastern Ukraine, not far from where the plane went down, as saying they had seized control of a missile defense army unit equipped with the Buk system.
Malaysian airliner downing puts spotlight on Buk missile system | Reuters
Had a serious diplomatic effort been underway to resolve the internal conflict, perhaps the tragedy might not have occurred. Such an opportunity was missed when insufficient pressure was placed on the parties to enact a ceasefire. Russia bears a lot of responsibility, as it should have made efforts to seal its border with Ukraine and made clear to the rebels that it expected them to enact a ceasefire.
The U.S. and EU should have urged Ukraine's government to be patient and try diplomacy before resorting to military operations. That didn't happen and the conflict intensified. Conflicts can and do often lead to unintended outcomes and other tragedies.
At the same time, international airlines should avoid conflict zones. Some had been avoiding eastern Ukraine, but others were not. The fact that a Ukrainian SU-27 fighter jet had been downed in recent days suggested that low-flying flights were not the only ones exposed to risk.
Hopefully, the party responsible (likely the rebels) will be held fully accountable for their actions.