Is it safe to operate over the prime sub-group of Curve25519?
Theoretically, yes you can do that. The idea you have is correct: we can simply choose an integer $k\in[1,p_1-1]$ to determine our public key $Q=[k]P$. The effective hardness in solving the discrete logarithm comes from the large prime order subgroup, so in that case we lose nothing.

However, it is not true that small sub-group attacks are not possible. We are still working over a curve $E$ which contains points of small order, let's say $P_2$ is a point of order 2. Now I engage in a Diffie-Hellman key exchange by sending over my (malicious) "public key" $P_2$. In turn I receive back $[k]P_2$, given that your secret key is $k$. Then 
$$k\equiv0\bmod{2}\iff [k]P_2=\mathcal{O}.$$
Hence I have learnt $k\bmod{2}$.

How should we prevent this? In the obvious way: before computing $[k]P_2$, we first check $8P_2\neq\mathcal{O}$. As poncho notes, this prevents only this specific attack. The more generalized attack, where we send $P_s=[k']P+Q_s$, for $Q_s$ a point of small order, still works and can instead be prevented by checking that $[p_1]P_s=\mathcal{O}$. As mentioned, this is quite expensive.

What we can do instead, is only allow our scalars to be $0\bmod{8}$ (i.e. the three lsb's all zero), so that there is nothing to be learnt in the first place. Therefore we have an inherent resistance against small sub-group attacks, which is not true if $k$ were prime. This is exactly what happens for Curve25519.