For there is one God and one mediator between God and mankind, the man Christ Jesus,
1 Timothy 2:5
Orthodox, Catholics and some Anglican Christians practice asking the departed saints to pray to God on their behalf, and Protestants frequently frown upon this practice. When criticizing the former, the latter will often appeal to this verse as a proof-text against it, saying "Jesus is the only mediator between God and man." It tends to be their go-to text.
However, a closer look at the text itself will show that the two points are not in opposition to each other in the least bit; the saints can still intercede for us, and Christ is still "the one mediator between God and man." This solution will be provided by citing the four preceding verses and the one following, and delving into the context of the word "mediator." The passage below is 1 Timothy 2:1-6
1 I urge, then, first of all, that petitions, prayers, intercession and thanksgiving be made for all people— 2 for kings and all those in authority, that we may live peaceful and quiet lives in all godliness and holiness. 3 This is good, and pleases God our Savior, 4 who wants all people to be saved and to come to a knowledge of the truth. 5 For there is one God and one mediator between God and mankind, the man Christ Jesus, 6 who gave himself as a ransom for all people...
What "One Mediator" Does Mean:
Verse 6 is especially important, because it describes what that office of mediator actually looks like and how it came to be. Jesus gave himself as a ransom for all people. In paying this ransom, Christ mediated our reconciliation with God the Father.
Reading the Epistle to the Hebrews sheds further light on the issue, because Hebrews equates Christ's office as mediator with his office as high priest of the people of God. Chapters five through ten expound on the nuances of His office as high priest and as mediator.
Every high priest is selected from among the people and is appointed to represent the people in matters related to God, to offer gifts and sacrifices for sins... During the days of Jesus’ life on earth, he offered up prayers and petitions with fervent cries and tears to the one who could save him from death, and he was heard because of his reverent submission. Son though he was, he learned obedience from what he suffered and, once made perfect, he became the source of eternal salvation for all who obey him and was designated by God to be high priest in the order of Melchizedek.
(Hebrews 5:1, 7-10)
Now there have been many of those priests, since death prevented them from continuing in office; but because Jesus lives forever, he has a permanent priesthood. Therefore he is able to save completely those who come to God through him, because he always lives to intercede for them.
Such a high priest truly meets our need—one who is holy, blameless, pure, set apart from sinners, exalted above the heavens. Unlike the other high priests, he does not need to offer sacrifices day after day, first for his own sins, and then for the sins of the people. He sacrificed for their sins once for all when he offered himself.
For this reason Christ is the mediator of a new covenant, that those who are called may receive the promised eternal inheritance—now that he has died as a ransom to set them free from the sins committed under the first covenant.
This last verse cited, IX, xv, directly equates Christ being mediator with his giving his life as a ransom. Other verses could be cited, but these will suffice. An high priest is appointed to represent the people in matters related to God, in offering gifts and sacrifices for sins. He lives always to intercede as a high priest, having sacrificed himself for their sins once for all. Jesus reconciled men unto God through the offering of His life. His sacrifice mediates forgiveness of sins, as is standard of His high priestly office. His mediation is on sacerdotal grounds, meaning that it is a covenantal mediation. It is something much more significant than simply praying on behalf of the people on earth -- this mediatorship encompasses the element of offering sacrifices, of remitting sin, of propitiating God the Father.
What "One Mediator" Doesn't Mean:
But, for the sake of argument, let's say that the word 'mediatior' described in 1 Tm 2:5 is written in an even more general sense and has a wider meaning than simply being the High Priest. Are we to understand it as forbidding intercessory prayer?
In verse 1 of this chapter, Paul urges that petitions, prayers, [and] intercessions be made for all people (the word intercession is specifically used.) If one wants to understand the concepts of intercessor and mediator as being synonymous, then St. Paul is contradicting himself. It is thus not coherent to read this verse as forbidding any and all intercessory prayer aside from that of Christ's.
Furthermore, Scripture itself testifies that the company of heaven do, in fact, pray for the holy ones on earth. The Book of Revelation depicts such an occurrence:
[. . .] the four living creatures and the twenty-four elders fell before the Lamb, each holding a harp and golden bowls full of incense, which are the prayers of the saintsHere, the twenty-four elders and four living creatures, who are present before the throne of God, present the prayers of the living to the Lamb of God. Paul's words thus cannot exclude this "mediation" which is here described; on the contrary: this intercession which Paul exhorts Timothy to is practiced by the hosts of heaven as well as by the saints upon earth.
One should take note also that it isn't even God the Father to which the incense of prayer is offered, but rather, to the Lamb: Christ, the priest and victim. The Father thus receives the prayers of both the earthly and heavenly saints through his Son. Even amidst the reality of heavenly intercessors, Jesus still stands out as "the one mediator between God and man."
In summary, Christ certainly is the "one mediator between God and man", in context of His high priesthood in Heaven, where He constantly beseeches His Father on behalf of His church, and this mediation is effective through surpassing value of His sacrifice on Calvary. There is nothing in asking the saints in heaven to pray for you which violates this principle -- ergo, there's no compromise in the truth set forth in 1 Timothy 2:5. Christ retains His rightful title and the honor it accords Him.