Question 1 : you probably use perl on the server side so 1 and 2 are kinda redundant. I think you will want to use a framework if you are not using one, because they do make building applications easier.
You will probably also want to look at the kind of code the server side will be running. If its only some crud then it should not take much resources but if each client represent a heavy calculation load then you might want to tune your code for performance when it comes to those calculations. If profiling and optimising is not enough then you might think about rewriting those parts in c/c++ (choice depending on the size of the program needed for said calculations, but choosing between c and c++ is an entirely different can of worms that I won't open here), ideally as a bunch of scriptable primitives.

On the database side, its something else entirely. What can be told depends greatly on what you know. What do you know about database management? ACID properties? What solution are you currently using?

you should start finding out how your current solution does when it comes to respecting them. Then again do some profiling, build indexes where they are needed, you probably wont have to rewrite your queries because most dbms nowadays have good optimizers... Basically you want the smallest possible transactions so you can do a bunch of them as fast as possible and easily recover from a database crash.

Previous paragraph assumes that your database is well designed, of course, if you have doubts on that topic then you might want to normalize it.