Tip no. 1:
Use route marking. Make a mangle rule that mark packets from your list with routing mark and stay away from routing table where the only route rule for all that addresses (route mark) is needed. No matter when and how you update the list only members of it would get the needed routing with no hickups
Tip no. 2:
The list that you prepare should be timebased so when you add an entry to it then you should set timer for the entry for eg. 6 hours if you refresh that list every 6 hours. When you readd the entry during that period you just refresh/reset that timer, if not the entry just vanishes. No need to worry of any leftovers.
Tip no. 3:
Read that “The International Microtik Obsfucated Code Contest” 
for updating address lists: http://forum.mikrotik.com/t/blacklist-filter-update-script/89817/385