This paper reports an exhaustive analysis performed over two specific Genetics-based Machine Learning systems: BioHEL and GAssist. These two systems share many mechanisms and operators, but at the same time, they apply two different learning paradigms (the Iterative Rule Learning approach and the Pittsburgh approach, respectively). The aim of this paper is to: (a) propose standard configurations for handling small and large datasets, (b) compare the two systems in terms of learning capabilities, complexity of the obtained solutions and learning time, (c) determine the areas of the problem space where each one of these two systems performs better, and (d) compare them with other well-known machine learning algorithms. The results show that it is possible to find standard configurations for both systems. With these configurations the systems perform up to the standards of other state-of-the-art machine learning algorithms such as Support Vector Machines. Moreover, we identify the problem domains where each one of these systems have advantages and disadvantages and propose ways to improve the systems based on this analysis.