Finding the large primes p and q is usually done by testing random numbers of the right size with probabilistic primality tests which quickly eliminate most non-primes. If such a test finds a "probable prime", a deterministic test should then be used to verify that the number is indeed prime.
p and q should not be 'too close', lest the Fermat factorization for N be successful. Furthermore, if either p-1 or q-1 has only small prime factors, N can be factored quickly and these values of p or q should therefore be discarded as well.
One should not employ a prime search method which gives any information whatsoever about the primes to the attacker. In particular, a good random number generator for the start value needs to be employed. Note that the requirement here is both 'random' and 'unpredictable'. These are not the same criteria; a number may have been chosen by a random process (i.e., no pattern in the results), but if it is predictable in any manner (or even partially predictable), the method used will result in loss of security. For example, the random number table published by the Rand Corp in the 1950s might very well be truly random, but it has been published and thus can serve an attacker as well. If the attacker can guess half of the digits of p or q, they can quickly compute the other half (shown by Coppersmith in 1997).
It is important that the secret key d be large enough. Wiener showed in 1990 that if p is between q and 2q (which is quite typical) and d < N1/4/3, then d can be computed efficiently from N and e. The encryption key e = 2 should also not be used.