In scripture, serpents are not usually seen as good. But it is common for an animal to be used both in a bad and good way. Here we are told to have this good characteristic.
In general, snakes are not the animal of choice. Who likes them? Many of them are dangerous. Many people will kill them if they come in contact with them (or near their house or family). You could say that snakes live in a “hostile environment”.
Jesus just told the disciples that they are going to be in a hostile environment (sheep among wolves).
Therefore, because of this hostile environment, snakes have to be wise. They have to be shrewd. The need a sharp sense of judgement. They pay attention, watch and can’t afford to be careless. In the same way, we need to have this sense of judgement as we enter our hostile environments preaching the Gospel.
“Serpents, being aware that they are hated, carefully avoid and shrink from every thing that is hostile to them. In this manner he enjoins believers to take care of their life, so as not to rush heedlessly into danger, or lay themselves open to any kind of injury.” 
Jesus gives an example of being wise. He tells the disciples if they are persecuted in one city, they should flee to another city.
We should be aware and alert to the danger that could happen. We shouldn’t we foolish and carefree.
We should have a “wise forwardness” with the gospel.
I think this commentator gives a second key aspect when he writes:
“Be therefore wise. The general meaning is, that their wisdom in exercising caution must be so regulated, as to prevent them from being more timid than is necessary, or from becoming more sluggish in duty. We see that those who wish to pass for cautious and circumspect persons are, for the most part, timorous and lazy. It is no doubt proper for the disciples of Christ, surrounded as they are by dangers on every hand, to maintain the strictest caution; but as they are in extreme danger of being kept back by slothfulness, he bids them move forward honestly wherever their calling leads them.” 
I think another good way to describe this “being wise” is “prudence”. A study of the “prudent man” in Proverbs will show this to be true (Proverbs 12:16, 23; 13:16; 14:8, 15, 18; 15:5; 16:21; 18:15; 22:3; 27:12).
If you mistranslate the verse, you go into hiding before the persecution even starts. You are willing to go on the mission but you aren’t preaching the message. You become foolish and lazy. You are disobedient to the command and you miss the chance to be a shining light through the God-ordained means of suffering for His name sake.