Simple Answer: For each $EXPTIME$-$hard$ problem there is some constant $c$ such that if we could solve the problem in $NTIME(2^{o(n^{\frac{1}{c}})})$, then $P \neq NP$.
Note: The constant $c$ comes from the instance size blow-ups that result from the reductions.
Justification: Let $X$ denote an $EXPTIME$-$hard$ problem. That means that every problem in $EXPTIME$ is polynomial time reducible to $X$. In fact, we can show more.
The acceptance problem for $2^n$ time bounded deterministic Turing machines is in $DTIME(n \cdot 2^n) \subseteq EXPTIME$ and therefore is polynomial time reducible to $X$.
Therefore, there must be some fixed constant $c$ such that every problem in $DTIME(2^n)$ is polynomial time reducible to $X$ where the instance size blow-up is $O(n^c)$. That is, instances of size n are reduced to instances of size $O(n^c)$ for $X$.
Now, if we had $X \in NTIME(2^{o(n^{\frac{1}{c}})})$, then $DTIME(2^n) \subseteq NTIME(2^{o(n)})$. However, this implies $P \neq NP$ (see below for details).
Additional Details: One can show that $P=NP$ $\Leftrightarrow$ $\exists c^{\prime}$ $\forall k$ $NTIME(n^k) \subseteq DTIME(n^{c^{\prime}k})$.
In other words, if you can solve an $NP$-$complete$ problem in polynomial time, then there is a uniform way of speeding up any problem in $NP$.
Now, let's suppose that $P=NP$. By the preceding (with $k$=1) we get a constant $c^{\prime}$ such that
$$NTIME(n) \subseteq DTIME(n^{c^{\prime}}).$$
Next, we can use padding to scale up this inclusion and get
$$NTIME(2^{n}) \subseteq DTIME(2^{c^{\prime}n}).$$
Then, by the deterministic time hierarchy theorem, we have
$$NTIME(2^{n}) \subseteq DTIME(2^{c^{\prime}n}) \subsetneq DTIME(2^{(c^{\prime}+\epsilon)n})$$
for any $\epsilon > 0$.
Therefore, we couldn't have
$DTIME(2^{(c^{\prime}+\epsilon)n}) \subseteq NTIME(2^{n}).$
Further, we couldn't have $DTIME(2^{n}) \subseteq NTIME(2^{o(n)})$ because by padding we would get $DTIME(2^{(c^{\prime}+\epsilon)n}) \subseteq NTIME(2^{o(n)})$.
Further Question: Does anyone have any simple examples of $EXPTIME$-$complete$ problems where we can easily determine the instance size blow-up constant $c$?