I feel like if they even try to follow an arc (they'd be stupid not to at this point, but that's beside the point), it would have to be Richard Dragon and the Longbow Hunters.

Some spoilers ahead, you've been warned.

Basically, Richard Dragon (aka Ricardo Diaz Jr.--he took the name Richard Dragon after murdering the original guy) is hellbent on revenge against the Green Arrow for murdering his father. In the comics, Diggle was dressed up as the Green Arrow and killed Ricardo Diaz Sr. during a mission. Basically, Dragon forms a villain team and puts a giant bounty on the Green Arrow's head.

Anyway, he has ties to the League of Assassins, and the "Longbow Hunters" consists of Brick, Clock King, Count Vertigo, Red Dart, and Killer Moth. 3/5 of these guys have been introduced to Arrow already, and the other two can either be introduced or substituted I'm sure.

Could easily reintroduce someone like Huntress or Chien Na Wei as parts of that--we haven't seen Chien Na Wei since season 3 when she kind of just disappeared without ever being discussed again.

There haven't really been MANY villains that I could suggest as a replacement--most of the major ones of the last 4 seasons have either been defeated, are more Flash-related, or were killed off (either for plot purposes, or because DC execs forced a death).

The only other previously introduced Arrow villains besides Huntress and Chien Na Wei I can really think of as replacements for Red Dart and Killer Moth would be: Anarky, Murmur, Cupid (Stupid!) or The Calculator--and of those, I think Murmur would really make the most sense (seeing as he worked previously with Brick to try and murder Noah Kuttler). So barring an E-2 counterpart coming over and being a villain, I think they're really stuck with those 6 choices.