The most obvious answer is perhaps Kyiv. Kyiv is the capital of Ukraine. It is located in the center of Ukraine on the country's largest river, Dnipro. Kyiv attracts the best and the brightest of Ukraine because of its job opportunities, universities, museums, etc. It was the capital of the Kyivan Rus, a medieval kingdom which many historians use as the start of Ukraine's history.
Kyiv is a fine answer, but I could see someone shooting holes in the argument as well. Kyiv is a city, not a region. Cities are easily manipulated and occupied by foreign powers compared to the countryside. This has been a common occurrence in Ukraine's history. Also, Kyiv was used by Vikings as a trading post. The Kyivan Rus was ruled by Scandinavian royalty who intermarried with the local population.
One of my students answered the heartland question with Lviv. He argued that Lviv is the cultural "heart" of Ukraine. The Ukrainian language is widely spoken there compared to other large cities in Ukraine. It is a city of artists and intellectuals. It was a historic locus for those who wanted to establish a Ukrainian state before independence in 1991.
But like Kyiv, Lviv is a city. Lviv is also historically diverse in terms of ethnicity, nationality, and religion. One could extend the traits of Lviv to the surrounding region of Halychyna, but Halychyna--as part of Austria-Hungary--was segregated from the rest of Ukraine behind a border for a very long time.
I hear that southern and eastern Ukraine are Ukraine's heartland less frequently. I usually make a point of bringing it up as a possible answer though. This was the core of the Cossack Hetmanate of the Zaporizhian Cossacks. The Cossacks stood up to the feudal system that existed at the time. As Timothy Snyder writes, "This political system brought the Cossack rebellion of 1648, in which free men who had escaped the system challenged its logic." The Cossacks and the land they rode horseback on, the Ukrainian steppe, was later romanticized by writers like Taras Shevchenko and Nikolai Gogal. Southern and eastern Ukraine--historic Zaporizhia--is therefore one of the key regions close to the heart of Ukraine's collective identity.
To see the disorder we are witnessing now in eastern Ukraine is tragic. Judging from history, foreign meddling in Ukraine seems to be a given by now. This is probably why there is no one place that can be called Ukraine's heartland. Ukraine's multiple heartlands have emerged in different places and at different times as a result of pressures from the foreign powers of the day. They become heartlands because of favorable or unfavorable conditions.
It's hard to say what will happen to Ukraine's borders in the near future. Will Russia just try to take Crimea? Donbas? All of Eastern Ukraine? Southern Ukraine? The whole country?
If any or all of these things happen, the newly redrawn borders will not last for long in my opinion. The Ukrainian nation has been established for a long time now, and it will only be a matter of time until Ukraine is whole again.
Please see the video below. It was filmed in Zaporizhia and shows the residents of that city standing up to Russian separatists. If Ukraine is divided, Russia will not cleave it neatly and naturally. It will most likely be a jagged and painful wound for the country.
On the bright side, all wounds heal.