I am running Pi-Hole like system assembled myself. OpenVPN, Tor, dnscrypt-proxy[3] and dnsmasq[2] plus large lists of blocks from Steven Black hosts project[1] and firehole.
I am running this for four years now in different incarnations and it is generally smooth. It was also quite educational to assemble.
[1] https://github.com/StevenBlack/hosts
[2] [3] dnsmasq isn't necessary as dnscypt-proxy is now able to block domains and IPs and of caching requests. I am using dnsmasq mostly for dhcp and to spread traffic among two dnscrypt-proxy clients and Google DNS.
Interesting. For the less tech savvy, is there a way to take the list on [1] and _automatically_ update the hosts file on my own machine (mac)?
Not automatically but you can use something such as Gasmask (https://github.com/2ndalpha/gasmask) to easily manage your host.