Yes, they are designed for multiple portals. Just bear in mind the licensing limit (Gold is 10 portals, Enterprise it up to 100).
It should not slow down noticeably, although I have never tried it on more than 10 portals at a time. The only factor will be 50 times more records in each table, so you are more likely to be constrained by database size, but this is a core/SQL issue, not a Smart-Thinker issue.